49 results on '"Dae Joong Kang"'
Search Results
2. Between ‘shopper’ and ‘owner’: emerging agency of lifelong learner in South Korea’s marketing-driven expansion of lifelong education
- Author
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Kyunglim Lee and Dae Joong Kang
- Subjects
Life-span and Life-course Studies ,Education - Published
- 2022
3. A Study on Identity Transition and Learning Activity of Local Activists from Labor Movement
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Min Sun Shin and Dae Joong Kang
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Movement (music) ,Transition (fiction) ,Identity (social science) ,Gender studies ,Sociology - Published
- 2021
4. The Development of Performance Management Indicators and Model for ‘Eup·Myeon·Dong Lifelong Learning Center’ : The Case of Seoul Metropolitan Government’s ‘Community Learning Center Project’
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Min Sun Shin, Dae Joong Kang, and Jisuk Park
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Metropolitan government ,Performance management ,business.industry ,Learning community ,Lifelong learning ,Center (algebra and category theory) ,Sociology ,Public relations ,business - Published
- 2020
5. Gut microbiota manipulation during the prepubertal period shapes behavioral abnormalities in a mouse neurodevelopmental disorder model
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Mikhail G. Dozmorov, Raquel Muñoz-Moreno, Masoumeh Sikaroodi, Swati Dalmet, Javier González-Maeso, Dae Joong Kang, Adolfo García-Sastre, Patrick M. Gillevet, Justin M. Saunders, José L. Moreno, Jasmohan S. Bajaj, and Daisuke Ibi
- Subjects
medicine.medical_specialty ,Offspring ,lcsh:Medicine ,Gut flora ,Article ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Neurodevelopmental disorder ,Memory ,Internal medicine ,medicine ,Animals ,Effects of sleep deprivation on cognitive performance ,Sexual Maturation ,lcsh:Science ,030304 developmental biology ,Problem Behavior ,0303 health sciences ,Pregnancy ,Multidisciplinary ,biology ,Behavior, Animal ,Disease model ,lcsh:R ,Age Factors ,Recognition, Psychology ,medicine.disease ,biology.organism_classification ,Anti-Bacterial Agents ,Gastrointestinal Microbiome ,Transplantation ,Disease Models, Animal ,Endocrinology ,Phenotype ,Schizophrenia ,Neurodevelopmental Disorders ,Autism ,lcsh:Q ,Disease Susceptibility ,Microbiome ,030217 neurology & neurosurgery - Abstract
Previous studies demonstrate an association between activation of the maternal immune system during pregnancy and increased risk of neurodevelopmental psychiatric conditions, such as schizophrenia and autism, in the offspring. Relatively recent findings also suggest that the gut microbiota plays an important role in shaping brain development and behavior. Here we show that maternal immune activation (MIA) accomplished by infection with a mouse-adapted influenza virus during pregnancy induced up-regulation of frontal cortex serotonin 5-HT2A receptor (5-HT2AR) density in the adult offspring, a phenotype previously observed in postmortem frontal cortex of schizophrenic subjects. 5-HT2AR agonist-induced head-twitch behavior was also augmented in this preclinical mouse model. Using the novel object recognition (NOR) test to evaluate cognitive performance, we demonstrate that MIA induced NOR deficits in adult offspring. Oral antibiotic treatment of prepubertal mice prevented this cognitive impairment, but not increased frontal cortex 5-HT2AR density or psychedelic-induced head-twitch behavior in adult MIA offspring. Additionally, gut microbiota transplantation from MIA mice produced behavioral deficits in antibiotic-treated mock mice. Adult MIA offspring displayed altered gut microbiota, and relative abundance of specific components of the gut microbiota, including Ruminococcaceae, correlated with frontal cortex 5-HT2AR density. Together, these findings provide a better understanding of basic mechanisms by which prenatal insults impact offspring brain function, and suggest gut-brain axis manipulation as a potential therapeutic approach for neurodevelopmental psychiatric conditions.
- Published
- 2020
6. Building Mechanism of Lifelong Learning
- Author
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Dae Joong Kang
- Subjects
Knowledge management ,Community education ,Community building ,business.industry ,Social cooperative ,Lifelong learning ,Sociology ,business ,Mechanism (sociology) - Published
- 2021
7. Disrupted, Ruptured, and in Between: Ruins of Schooling and Utopian Learning Society
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Dae Joong Kang
- Subjects
Industry 4.0 ,Coronavirus disease 2019 (COVID-19) ,Information and Communications Technology ,Social distance ,Scale (social sciences) ,Lifelong learning ,ComputingMilieux_COMPUTERSANDEDUCATION ,Learning society ,Environmental ethics ,Sociology ,Global education - Abstract
This chapter presents an overview of the disrupted school-centered education system and the emerging new normal in the coronavirus disease (COVID-19) pandemic. Enforced social distancing and school closures made technology-enhanced education a reality on an unprecedented scale for the first time in history. Various information and communication technologies provide a solution to the global education crisis. The author revisits the landmark 1972 Faure report to remind us that recognizing fast technological development was the background of the learning society proposal. Technology always brings about a profound challenge in education. The concept of a learning society has paved the unavoidable direction of educational change from universal schooling to lifelong learning. While there are different understandings of lifelong learning and learning society, the author points out that we are indeed in the middle of the second educational revolution heading toward the lifelong learning era. The author argues that we need to take advantage of the COVID-19 pandemic to make creative and imaginative policy proposals, which can accelerate the realization of the learning society.
- Published
- 2021
8. ADAM10 regulates transcription factor expression required for plasma cell function.
- Author
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Natalia S Chaimowitz, Dae-Joong Kang, Lee M Dean, and Daniel H Conrad
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Medicine ,Science - Abstract
A disintegrin and metalloprotease 10 (ADAM10) is a key regulator of cellular processes by shedding extracellular domains of transmembrane proteins. We have previously demonstrated that deletion of B cell expressed ADAM10 results in changes in lymphoid tissue architecture and impaired germinal center (GC) formation. In this study, mice were generated in which ADAM10 is deleted in B cells following class switch recombination (ADAM10(Δ/Δ)IgG1-cre(+/-) mice). Despite normal GC formation, antibody responses were impaired in ADAM10(Δ/Δ)IgG1-cre(+/-) mice, implicating ADAM10 in post-GC and extrafollicular B cell terminal differentiation. Surprisingly, plasma cell (PC) numbers were normal in ADAM10(Δ/Δ)IgG1-cre(+/-) mice when compared to controls. However, PCs isolated from ADAM10(Δ/Δ)IgG1-cre(+/-) mice exhibited decreased expression of transcription factors important for PC function: Prdm1, Xbp1 and Irf4. Bcl6 is a GC transcriptional repressor that inhibits the PC transcriptional program and thus must be downregulated for PC differentiation to occur. Bcl6 expression was increased in PCs isolated from ADAM10(Δ/Δ)IgG1-cre(+/-) mice at both the mRNA and protein level. These results demonstrate that ADAM10 is required for proper transcription factor expression in PCs and thus, for normal PC function.
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- 2012
- Full Text
- View/download PDF
9. Continued Alcohol Misuse in Human Cirrhosis is Associated with an Impaired Gut-Liver Axis
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Masoumeh Sikaroodi, Edith Gavis, Mary L. Holtz, Derrick Zhao, Runping Liu, Pippa Simpson, Oliver Fiehn, Patrick M. Gillevet, Genta Kakiyama, Dae Joong Kang, William M. Pandak, Hiroshi Nittono, Andrew Fagan, Douglas M. Heuman, Phillip B. Hylemon, Huiping Zhou, Hajime Takei, Nita H. Salzman, and Jasmohan S. Bajaj
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Liver Cirrhosis ,Male ,0301 basic medicine ,medicine.medical_specialty ,Cirrhosis ,medicine.drug_class ,medicine.medical_treatment ,Medicine (miscellaneous) ,Inflammation ,Ileum ,Biology ,Toxicology ,Systemic inflammation ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Endoscopy, Digestive System ,Bile acid ,Microbiota ,Middle Aged ,medicine.disease ,Gastrointestinal Tract ,Alcoholism ,Psychiatry and Mental health ,030104 developmental biology ,medicine.anatomical_structure ,Cytokine ,Duodenum ,Dysbiosis ,Female ,030211 gastroenterology & hepatology ,medicine.symptom - Abstract
Background Cirrhosis and alcohol can independently affect the gut–liver axis with systemic inflammation. However, their concurrent impact in humans is unclear. Methods Our aim was to determine the effect of continued alcohol misuse on the gut-liver axis in cirrhotic patients. Age- and MELD-balanced cirrhotic patients who were currently drinking (Alc) or abstinent (NAlc) and healthy controls underwent serum and stool collection. A subset underwent upper endoscopy and colonoscopy for biopsies and duodenal fluid collection. The groups were compared regarding (i) inflammation/intestinal barrier: systemic tumor necrosis factor levels, intestinal inflammatory cytokine (duodenum, ileum, sigmoid), and ileal antimicrobial peptide expression; (ii) microbiota composition: 16SrRNA sequencing of duodenal, ileal, and colonic mucosal and fecal microbiota; and (iii) microbial functionality: duodenal fluid and fecal bile acid (BA) profile (conjugation and dehydroxylation status), intestinal BA transporter (ASBT, FXR, FGF-19, SHP) expression, and stool metabolomics using gas chromatography/mass spectrometry. Results Alc patients demonstrated a significant duodenal, ileal, and colonic mucosal and fecal dysbiosis, compared to NAlc and controls with lower autochthonous bacterial taxa. BA profile skewed toward a potentially toxic profile (higher secondary and glycine-conjugated BAs) in duodenal fluid and stool in Alc patients. Duodenal fluid demonstrated conjugated secondary BAs only in the Alc group. There was a greater expression of all ileal BA transporters in Alc patients. This group also showed higher endotoxemia, systemic and ileal inflammatory expression, and lower amino acid and bioenergetic-associated metabolites, without change in antimicrobial peptide expression. Conclusions Despite cirrhosis, continued alcohol misuse predisposes patients to widespread dysbiosis with alterations in microbial functionality such as a toxic BA profile, which can lead to intestinal and systemic inflammation.
- Published
- 2017
10. Lost in travel or a different conception? (Mis-)appropriation of transformative learning theory in the Republic of Korea
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Sungmin Cho and Dae Joong Kang
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05 social sciences ,Lifelong learning ,050301 education ,The Republic ,Education ,Epistemology ,Chose ,Appropriation ,Transformative learning ,0502 economics and business ,Learning theory ,Western culture ,Sociology ,Social science ,Sociocultural evolution ,0503 education ,050203 business & management - Abstract
Theoretical thought on adult and/or lifelong learning in the Republic of Korea has been largely indebted to Western theoretical frameworks in the past few decades. Academic journal articles and doctoral dissertations dealing with the topic of learning in adulthood flooded with Western, typically North American, theories and concepts. Is it indeed unproblematic to use Western frameworks in understanding domestic phenomena of learning in adulthood? To tackle this question, we looked into 15 academic journal articles in the Republic of Korea, which are explicitly taking Jack Mezirow’s transformative learning theory as a theoretical framework. We chose Mezirow’s theory because its undoubted status as a solid theory has recently faced serious challenge in Western scholarly communities. In the analysis of the chosen journal articles, we focus on how those articles used Mezirow’s theory in terms of its core elements. We concluded that Mezirow’s theory has been largely misappropriated. We used Edward Said’s concept of “traveling theory” to discuss possible reasons for this (mis-)appropriation. We suggested that sociocultural and historical influence should be taken into consideration in theory-use as well as theory-making.
- Published
- 2017
11. Salivary microbiota reflects changes in gut microbiota in cirrhosis with hepatic encephalopathy
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Masoumeh Sikaroodi, Melanie B. White, Patrick M. Gillevet, Leroy R. Thacker, Kalyani Daita, Arun J. Sanyal, Phillip B. Hylemon, Ariel Unser, Dae Joong Kang, Douglas M. Heuman, Jasmohan S. Bajaj, and Naga S. Betrapally
- Subjects
Liver Cirrhosis ,Male ,Saliva ,Cirrhosis ,Hepatology ,Gastrointestinal Microbiome ,Biology ,Gut flora ,medicine.disease ,Systemic inflammation ,biology.organism_classification ,Article ,Intestines ,Feces ,Hepatic Encephalopathy ,Immunology ,medicine ,Humans ,Female ,Oral Microbiome ,Microbiome ,medicine.symptom ,Dysbiosis - Abstract
Altered gut microbiome is associated with systemic inflammation and cirrhosis decompensation. However, the correlation of the oral microbiome with inflammation in cirrhosis is unclear. Our aim was to evaluate the oral microbiome in cirrhosis and compare with stool microbiome. Outpatients with cirrhosis (with/without hepatic encephalopathy [HE]) and controls underwent stool/saliva microbiome analysis (for composition and function) and also systemic inflammatory evaluation. Ninety-day liver-related hospitalizations were recorded. Salivary inflammation was studied using T helper 1 cytokines/secretory immunoglobulin A (IgA), histatins and lysozyme in a subsequent group. A total of 102 patients with cirrhosis (43 previous HE) and 32 age-matched controls were included. On principal component analysis (PCA), stool and saliva microbiome clustered far apart, showing differences between sites as a whole. In salivary microbiome, with previous HE, relative abundance of autochthonous families decreased whereas potentially pathogenic ones (Enterobacteriaceae, Enterococcaceae) increased in saliva. Endotoxin-related predicted functions were significantly higher in cirrhotic saliva. In stool microbiome, relative autochthonous taxa abundance reduced in previous HE, along with increased Enterobacteriaceae and Enterococcaceae. Cirrhotic stool microbiota demonstrated a significantly higher correlation with systemic inflammation, compared to saliva microbiota, on correlation networks. Thirty-eight patients were hospitalized within 90 days. Their salivary dysbiosis was significantly worse and predicted this outcome independent of cirrhosis severity. Salivary inflammation was studied in an additional 86 age-matched subjects (43 controls/43 patients with cirrhosis); significantly higher interleukin (IL)−6/IL-1β, secretory IgA, and lower lysozyme, and histatins 1 and 5 were found in patients with cirrhosis, compared to controls. Conclusions: Dysbiosis, represented by reduction in autochthonous bacteria, is present in both saliva and stool in patients with cirrhosis, compared to controls. Patients with cirrhosis have impaired salivary defenses and worse inflammation. Salivary dysbiosis was greater in patients with cirrhosis who developed 90-day hospitalizations. These findings could represent a global mucosal-immune interface change in cirrhosis. (Hepatology 2015;62:1260-1271)
- Published
- 2015
12. Emergence of informal educative space out of an anonymous online bulletin board in Korea during the global economic crisis
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SeungHyeop Lee, Seon Joo Choi, and Dae Joong Kang
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Concept map ,business.industry ,Informal education ,Informal learning ,Public relations ,Education ,Bulletin board ,Content analysis ,Pedagogy ,Agora ,Sociology ,Computer-mediated communication ,Life-span and Life-course Studies ,business ,computer ,computer.programming_language ,Qualitative research - Abstract
This study aimed to understand how people learn and teach informally in an anonymous online bulletin board, the primary purpose of which is not learning and teaching. We conducted a qualitative analysis of comments and replies tagged to the most popular postings of an anonymous online bulletin board, during the global economic crisis in 2008–2009. The bulletin board, Agora Economy Room, is housed in the Korean portal site, Daum. We found four interrelated collective activities—recognizing teaching presence, collaborating, labeling, and guarding—among the participants that made active informal learning and teaching possible. These activities had an effect on the characteristics of the emerging informal educative space in different ways. A conceptual map of the findings of this study is discussed as a conclusion.
- Published
- 2013
13. A Study on the Reliability Prediction about ECM of Packaging Substrate PCB by Using Accelerated Life Test
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Dae-Joong Kang and Hwa-Ki Lee
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Electrochemical migration ,Acceleration ,Engineering ,Substrate (building) ,Reliability (semiconductor) ,business.industry ,Electronics ,business ,Weibull distribution ,Reliability engineering ,Voltage ,Accelerated life testing - Abstract
As information-oriented industry has been developed and electronic devices has come to be smaller, lighter, multifunctional, and high speed, the components used to the devices need to be much high density and should have find pattern due to high integration. Also, diverse reliability problems happen as user environment is getting harsher. For this reasons, establishing and securing products and components reliability comes to key factor in company`s competitiveness. It makes accelerated test important to check product reliability in fast way. Out of fine pattern failure modes, failure of Electrochemical Migration(ECM) is kind of degradation of insulation resistance by electro-chemical reaction, which it comes to be accelerated by biased voltage in high temperature and high humidity environment. In this thesis, the accelerated life test for failure caused by ECM on fine pattern substrate, pattern width/space applied by Semi Additive Process, was performed, and through this test, the investigation of failure mechanism and the life-time prediction evaluation under actual user environment was implemented. The result of accelerated test has been compared and estimated with life distribution and life stress relatively by using Minitab software and its acceleration rate was also tested. Through estimated weibull distribution, B10 life has been estimated under 95% confidence level of failure data happened in each test conditions. And the life in actual usage environment has been predicted by using generalized Eyring model considering temperature and humidity by developing Arrhenius reaction rate theory, and acceleration factors by test conditions have been calculated.
- Published
- 2013
14. Creating learning: a korean drummer's lifelong quest to be the best
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Dae Joong Kang
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Adult education -- Methods ,Continuing education -- Methods ,Psychology and mental health - Published
- 2010
15. Life and Learning of Korean Artists and Craftsmen : Rhizoactivity
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Dae Joong Kang and Dae Joong Kang
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- Adult learning--Korea (South), Continuing education--Korea (South), Educational sociology--Korea (South), Artists--Education--Korea (South), Artisans--Education--Korea (South), EDUCATION / Adult & Continuing Education, EDUCATION / Non-Formal Education, SOCIAL SCIENCE / Regional Studies
- Abstract
This book brings out the need for lifelong learning theory and explores how it is possible from a postmodern perspective. The book uses life history that has gained its popularity in social science research to overcome the dichotomy between individual and society or between agency and structure. Life history also reflects the postmodern or late-modern conditions of social life. In this book, the author uses a collection of published oral history narratives of famous Korean artists and craftsmen. The author maps out life and learning of five such artists and craftsmen with figurations of escaping, creating, controlling and formalizing. These figurations are images of ‘Rhizoactivity'that the author proposes as a new conceptual tool to navigate lifelong learning from a postmodern perspective. This book signalises a new way of theory building in the field of adult and lifelong education. The Life and Learning of Korean Artists and Craftsmen: Rhizoactivity conceptualises: Adult learning in terms of postmodern and lifelong learning conditions Life histories as a method of researching lifelong learning The four facets of artistic journeys – escaping, creating, controlling and formalizing This book will interest researchers focusing on lifelong and adult education. Its use of social theories in its study of lifelong learning amongst Korean artists will also interest sociologists and educators concerned with the sociology of education.
- Published
- 2015
16. Gut microbial composition can differentially regulate bile acid synthesis in humanized mice
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Hiroshi Nittono, Jing Yang, Naga S. Betrapally, Patrick M. Gillevet, Chunhua Jiao, Hajime Takei, William M. Pandak, Phillip B. Hylemon, Douglas M. Heuman, Huiping Zhou, Masoumeh Sikaroodi, Xiaojiaoyang Li, Genta Kakiyama, R. Balfour Sartor, Jasmohan S. Bajaj, H. Robert Lippman, and Dae Joong Kang
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Cirrhosis ,medicine.drug_class ,Gut flora ,Cholesterol 7 alpha-hydroxylase ,Gastroenterology ,digestive system ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Internal medicine ,medicine ,2. Zero hunger ,Messenger RNA ,Hepatology ,biology ,Bile acid ,Chemistry ,Cholesterol ,Original Articles ,biology.organism_classification ,medicine.disease ,030104 developmental biology ,Endocrinology ,Small heterodimer partner ,030211 gastroenterology & hepatology ,Original Article ,CYP8B1 - Abstract
We previously reported that alcohol drinkers with and without cirrhosis showed a significant increase in fecal bile acid secretion compared to nondrinkers. We hypothesized this may be due to activation by alcohol of hepatic cyclic adenosine monophosphate responsive element-binding protein 3-like protein 3 (CREBH), which induces cholesterol 7α-hydroxylase (Cyp7a1). Alternatively, the gut microbiota composition in the absence of alcohol might increase bile acid synthesis by up-regulating Cyp7a1. To test this hypothesis, we humanized germ-free (GF) mice with stool from healthy human subjects (Ctrl-Hum), human subjects with cirrhosis (Cirr-Hum), and human subjects with cirrhosis and active alcoholism (Alc-Hum). All animals were fed a normal chow diet, and none demonstrated cirrhosis. Both hepatic Cyp7a1 and sterol 12α-hydroxylase (Cyp8b1) messenger RNA (mRNA) levels were significantly induced in the Alc-Hum and Ctrl-Hum mice but not in the Cirr-Hum mice or GF mice. Liver bile acid concentration was correspondingly increased in the Alc-Hum mice despite fibroblast growth factor 15, fibroblast growth receptor 4, and small heterodimer partner mRNA levels being significantly induced in the large bowel and liver of the Ctrl-Hum mice and Alc-Hum mice but not in the Cirr-Hum mice or GF mice. This suggests that the normal pathways of Cyp7a1 repression were activated in the Alc-Hum mice and Ctrl-Hum mice. CREBH mRNA was significantly induced only in the Ctrl-Hum mice and Alc-Hum mice, possibly indicating that the gut microbiota up-regulate CREBH and induce bile acid synthesis genes. Analysis of stool bile acids showed that the microbiota of the Cirr-Hum and Alc-Hum mice had a greater ability to deconjugate and 7α-dehydroxylate primary bile acids compared to the microbiota of the Cirr-Hum mice. 16S ribosomal RNA gene sequencing of the gut microbiota showed that the relative abundance of taxa that 7-α dehydroxylate primary bile acids was higher in the Ctrl-Hum and Alc-Hum groups. Conclusion: The composition of gut microbiota influences the regulation of the rate-limiting enzymes in bile acid synthesis in the liver. (Hepatology Communications 2017;1:61-70).
- Published
- 2016
17. Gut microbiota drive the development of neuroinflammatory response in cirrhosis in mice
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Patrick M. Gillevet, Phillip B. Hylemon, Huiping Zhou, Masoumeh Sikaroodi, Arun J. Sanyal, Siddhartha A. Ghosh, Dae Joong Kang, Chunhua Jiao, Douglas M. Heuman, Jing Yang, H. Robert Lippman, Runping Liu, Robert R. Brown, Xiang Wang, R. Balfour Sartor, Jasmohan S. Bajaj, Jeremy Herzog, Daniel E. Carl, and Naga S. Betrapally
- Subjects
0301 basic medicine ,Liver Cirrhosis ,Inflammation ,Biology ,Gut flora ,Systemic inflammation ,Glutaminase activity ,Article ,Proinflammatory cytokine ,03 medical and health sciences ,Mice ,0302 clinical medicine ,medicine ,Animals ,Hyperammonemia ,Neuroinflammation ,Hepatology ,medicine.disease ,biology.organism_classification ,Gastrointestinal Microbiome ,Glutamine ,Mice, Inbred C57BL ,030104 developmental biology ,Immunology ,030211 gastroenterology & hepatology ,medicine.symptom ,Neuroglia - Abstract
The mechanisms behind the development of hepatic encephalopathy (HE) are unclear, although hyperammonemia and systemic inflammation through gut dysbiosis have been proposed. The aim of this work was to define the individual contribution of hyperammonemia and systemic inflammation on neuroinflammation in cirrhosis using germ-free (GF) and conventional mice. GF and conventional C57BL/6 mice were made cirrhotic using CCl4 gavage. These were compared to their noncirrhotic counterparts. Intestinal microbiota, systemic and neuroinflammation (including microglial and glial activation), serum ammonia, intestinal glutaminase activity, and cecal glutamine content were compared between groups. GF cirrhotic mice developed similar cirrhotic changes to conventional mice after 4 extra weeks (16 vs. 12 weeks) of CCl4 gavage. GF cirrhotic mice exhibited higher ammonia, compared to GF controls, but this was not associated with systemic or neuroinflammation. Ammonia was generated through increased small intestinal glutaminase activity with concomitantly reduced intestinal glutamine levels. However, conventional cirrhotic mice had intestinal dysbiosis as well as systemic inflammation, associated with increased serum ammonia, compared to conventional controls. This was associated with neuroinflammation and glial/microglial activation. Correlation network analysis in conventional mice showed significant linkages between systemic/neuroinflammation, intestinal microbiota, and ammonia. Specifically beneficial, autochthonous taxa were negatively linked with brain and systemic inflammation, ammonia, and with Staphylococcaceae, Lactobacillaceae, and Streptococcaceae. Enterobacteriaceae were positively linked with serum inflammatory cytokines. Conclusion: Gut microbiota changes drive development of neuroinflammatory and systemic inflammatory responses in cirrhotic animals. (Hepatology 2016;64:1232-1248)
- Published
- 2016
18. Erratum: Gut Microbiota Alterations can predict Hospitalizations in Cirrhosis Independent of Diabetes Mellitus
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Jasmohan S. Bajaj, Naga S. Betrapally, Phillip B. Hylemon, Leroy R. Thacker, Kalyani Daita, Dae Joong Kang, Melanie B. White, Ariel B. Unser, Andrew Fagan, Edith A. Gavis, Masoumeh Sikaroodi, Swati Dalmet, Douglas M. Heuman, and Patrick M. Gillevet
- Subjects
Multidisciplinary - Abstract
Diabetes (DM) is prevalent in cirrhosis and may modulate the risk of hospitalization through gut dysbiosis. We aimed to define the role of gut microbiota on 90-day hospitalizations and of concomitant DM on microbiota. Cirrhotic outpatients with/without DM underwent stool and sigmoid mucosal microbial analysis and were followed for 90 days. Microbial composition was compared between those with/without DM, and those who were hospitalized/not. Regression/ROC analyses for hospitalizations were performed using clinical and microbial features. 278 cirrhotics [39% hepatic encephalopathy (HE), 31%DM] underwent stool while 72 underwent mucosal analyses. Ultimately, 94 were hospitalized and they had higher MELD, proton pump inhibitor (PPI) use and HE without difference in DM. Stool/mucosal microbiota were significantly altered in those who were hospitalized (UNIFRAC pBacteroidaceae, Clostridiales XIV, Lachnospiraceae, Ruminococcacae and higher Enterococcaceae and Enterobacteriaceae were seen in hospitalized patients. Concomitant DM impacted microbiota UNIFRAC (stool, p = 0.003, mucosa,p = 0.04) with higher stool Bacteroidaceae and lower Ruminococcaeae. Stool Bacteroidaceaeae and Clostridiales XIV predicted 90-day hospitalizations independent of clinical predictors (MELD, HE, PPI). Stool and colonic mucosal microbiome are altered in cirrhotics who get hospitalized with independent prediction using stool Bacteroidaceae and Clostridiales XIV. Concomitant DM distinctly impacts gut microbiota without affecting hospitalizations.
- Published
- 2016
19. Gut Microbiota Alterations can predict Hospitalizations in Cirrhosis Independent of Diabetes Mellitus
- Author
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Kalyani Daita, Phillip B. Hylemon, Masoumeh Sikaroodi, Andrew Fagan, Naga S. Betrapally, Swati Dalmet, Douglas M. Heuman, Dae Joong Kang, Jasmohan S. Bajaj, Leroy R. Thacker, Patrick M. Gillevet, Edith Gavis, Ariel Unser, and Melanie B. White
- Subjects
Liver Cirrhosis ,Male ,medicine.medical_specialty ,Cirrhosis ,Gut flora ,Gastroenterology ,Article ,Feces ,03 medical and health sciences ,0302 clinical medicine ,fluids and secretions ,Intestinal mucosa ,Internal medicine ,medicine ,Humans ,Microbiome ,Intestinal Mucosa ,Bacteroidaceae ,Hepatic encephalopathy ,Demography ,030304 developmental biology ,Principal Component Analysis ,0303 health sciences ,Multidisciplinary ,biology ,business.industry ,Clostridiales ,Lachnospiraceae ,digestive, oral, and skin physiology ,Middle Aged ,biology.organism_classification ,medicine.disease ,Gastrointestinal Microbiome ,3. Good health ,Hospitalization ,Logistic Models ,Treatment Outcome ,Diabetes Mellitus, Type 2 ,Female ,030211 gastroenterology & hepatology ,Erratum ,business - Abstract
Diabetes (DM) is prevalent in cirrhosis and may modulate the risk of hospitalization through gut dysbiosis. We aimed to define the role of gut microbiota on 90-day hospitalizations and of concomitant DM on microbiota. Cirrhotic outpatients with/without DM underwent stool and sigmoid mucosal microbial analysis and were followed for 90 days. Microbial composition was compared between those with/without DM and those who were hospitalized/not. Regression/ROC analyses for hospitalizations were performed using clinical and microbial features. 278 cirrhotics [39% hepatic encephalopathy (HE), 31%DM] underwent stool while 72 underwent mucosal analyses. Ultimately, 94 were hospitalized and they had higher MELD, proton pump inhibitor (PPI) use and HE without difference in DM. Stool/mucosal microbiota were significantly altered in those who were hospitalized (UNIFRAC pBacteroidaceae, Clostridiales XIV, Lachnospiraceae, Ruminococcacae and higher Enterococcaceae and Enterobacteriaceae were seen in hospitalized patients. Concomitant DM impacted microbiota UNIFRAC (stool, p = 0.003, mucosa,p = 0.04) with higher stool Bacteroidaceae and lower Ruminococcaeae. Stool Bacteroidaceaeae and Clostridiales XIV predicted 90-day hospitalizations independent of clinical predictors (MELD, HE, PPI). Stool and colonic mucosal microbiome are altered in cirrhotics who get hospitalized with independent prediction using stool Bacteroidaceae and Clostridiales XIV. Concomitant DM distinctly impacts gut microbiota without affecting hospitalizations.
- Published
- 2015
- Full Text
- View/download PDF
20. Erratum to: Lost in travel or a different conception? (Mis-)appropriation of transformative learning theory in the Republic of Korea
- Author
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Dae Joong Kang and Sungmin Cho
- Subjects
Education - Published
- 2017
21. A Disintegrin and Metalloproteinase 10 Regulates Antibody Production and Maintenance of Lymphoid Architecture
- Author
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Natalia S. Chaimowitz, Joanna Cichy, Julie Farnsworth, Brent McCright, Eugene C. Butcher, Rebecca K. Martin, Dae-Joong Kang, David R. Gibb, Daniel H. Conrad, and Pooja Patil
- Subjects
Chemokine ,ADAM10 ,T cell ,Immunology ,B-Lymphocyte Subsets ,Mice, Transgenic ,Spleen ,CHO Cells ,Lymphocyte Activation ,Article ,ADAM10 Protein ,Mice ,Peyer's Patches ,T-Lymphocyte Subsets ,Cell surface receptor ,Cricetinae ,medicine ,Disintegrin ,Animals ,Immunology and Allergy ,Mice, Knockout ,Mice, Inbred BALB C ,Follicular dendritic cells ,biology ,Membrane Proteins ,Germinal center ,Germinal Center ,Molecular biology ,Immunity, Humoral ,Up-Regulation ,ADAM Proteins ,medicine.anatomical_structure ,biology.protein ,Amyloid Precursor Protein Secretases - Abstract
A disintegrin and metalloproteinase 10 (ADAM10) is a zinc-dependent proteinase related to matrix metalloproteinases. ADAM10 has emerged as a key regulator of cellular processes by cleaving and shedding extracellular domains of multiple transmembrane receptors and ligands. We have developed B cell-specific ADAM10-deficient mice (ADAM10B−/−). In this study, we show that ADAM10 levels are significantly enhanced on germinal center B cells. Moreover, ADAM10B−/− mice had severely diminished primary and secondary responses after T-dependent immunization. ADAM10B−/− displayed impaired germinal center formation, had fewer follicular Th cells, decreased follicular dendritic cell networks, and altered chemokine expression in draining lymph nodes (LNs). Interestingly, when spleen and LN structures from immunized mice were analyzed for B and T cell localization, tissues structure was aberrant in ADAM10B−/− mice. Importantly, when ADAM10-deficient B cells were stimulated in vitro, they produced comparable Ab as wild type B cells. This result demonstrates that the defects in humoral responses in vivo result from inadequate B cell activation, likely because of the decrease in follicular Th cells and the changes in structure. Thus, ADAM10 is essential for the maintenance of lymphoid structure after Ag challenge.
- Published
- 2011
22. A potential new target for asthma therapy: A Disintegrin and Metalloprotease 10 (ADAM10) involvement in murine experimental asthma
- Author
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Anthony Dellinger, Peggy Scherle, David R. Gibb, Andrew Q. Ford, Achsah D. Keegan, Christopher L. Kepley, Sarah K. Norton, Jill Ford, Joel A. Mathews, Daniel H. Conrad, Dae-Joong Kang, and Hugh Massay
- Subjects
Chemokine ,Lung ,biology ,medicine.medical_treatment ,ADAM10 ,Immunology ,CD23 ,Inflammation ,respiratory system ,Immunoglobulin E ,respiratory tract diseases ,Cytokine ,medicine.anatomical_structure ,biology.protein ,medicine ,Immunology and Allergy ,Eosinophilia ,medicine.symptom - Abstract
Background: Elevated levels of CD23, a natural regulator of IgE production, have been shown to decrease the signs of lung inflammation in mice. The aim of this study was to study the involvement of ADAM10, the primary CD23 sheddase, in experimental asthma. Methods: ADAM10 was blocked either by using mice with a B-cell-specific deletion of the protease or pharmacologically by intranasal administration of selective ADAM10 inhibitors. Airway hypersensitivity (AHR) and bronchoaveolar lavage fluid (BALF) eosinophilia and select BALF cytokine/chemokine levels were then determined. Results: Using an IgE and mast cell–dependent mouse model, B-cell-specific ADAM10-/- mice (C57B/6 background) exhibited decreased eosinophilia and AHR when compared with littermate (LM) controls. Treatment of C57B/6 mice with selective inhibitors of ADAM10 resulted in an even further decrease in BALF eosinophilia, as compared with the ADAM10-/- animals. Even in the Th2 selective strain, Balb/c, BALF eosinophilia was reduced from 60% to 23% respectively. In contrast, when an IgE/mast cell–independent model of lung inflammation was used, the B-cell ADAM10-/- animals and ADAM10 inhibitor treated animals had lung inflammation levels that were similar to the controls. Conclusions: These results thus show that ADAM10 is important in the progression of IgE-dependent lung inflammation. The use of the inhibitor further suggested that ADAM10 was important for maintaining Th2 levels in the lung. These results thus suggest that decreasing ADAM10 activity could be beneficial in controlling asthma and possibly other IgE-dependent diseases.
- Published
- 2011
23. ADAM10 Overexpression Shifts Lympho- and Myelopoiesis by Dysregulating Site 2/Site 3 Cleavage Products of Notch
- Author
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Daniel H. Conrad, Dae-Joong Kang, Sheinei J. Saleem, David R. Gibb, and Mark A. Subler
- Subjects
Myeloid ,Stromal cell ,T cell ,Immunology ,Notch signaling pathway ,Mice, Transgenic ,Thymus Gland ,Biology ,Cleavage (embryo) ,Article ,ADAM10 Protein ,Mice ,medicine ,Animals ,Immunology and Allergy ,Cell Lineage ,Cells, Cultured ,Myeloid Progenitor Cells ,B cell ,Cell Proliferation ,Myelopoiesis ,B-Lymphocytes ,Receptors, Notch ,Cell growth ,Hydrolysis ,Lymphopoiesis ,Multipotent Stem Cells ,Membrane Proteins ,Hematopoietic Stem Cells ,Growth Inhibitors ,Cell biology ,Mice, Inbred C57BL ,ADAM Proteins ,medicine.anatomical_structure ,Amyloid Precursor Protein Secretases ,Signal Transduction - Abstract
Although the physiological consequences of Notch signaling in hematopoiesis have been extensively studied, the differential effects of individual notch cleavage products remain to be elucidated. Given that ADAM10 is a critical regulator of Notch and that its deletion is embryonically lethal, we generated mice that overexpress ADAM10 (ADAM10 transgenic [A10Tg]) at early stages of lympho- and myeloid development. Transgene expression resulted in abrogated B cell development, delayed T cell development in the thymus, and unexpected systemic expansion of CD11b+Gr-1+ cells, also known as myeloid-derived suppressor cells. Mixed bone marrow reconstitution assays demonstrated that transgene expression altered hematopoiesis via a cell-intrinsic mechanism. Consistent with previously reported observations, we hypothesized that ADAM10 overexpression dysregulated Notch by uncoupling the highly regulated proteolysis of Notch receptors. This was confirmed using an in vitro model of hematopoiesis via culturing A10Tg hematopoietic Lineage−Sca-1+c-Kit+ cells with OP-9 stromal cells in the presence or absence of Delta-like 1, a primary ligand for Notch. Blockade of the site 2 (S2) and site 3 (S3) cleavage of the Notch receptor demonstrated differential effects on hematopoiesis. OP9-DL1 cultures containing the ADAM10 inhibitor (S2 cleavage site) enhanced and rescued B cell development from wild-type and A10Tg Lineage−Sca-1+c-Kit+ cells, respectively. In contrast, blockade of γ-secretase at the S3 cleavage site induced accumulation of the S2 product and consequently prevented B cell development and resulted in myeloid cell accumulation. Collectively, these findings indicate that the differential cleavage of Notch into S2 and S3 products regulated by ADAM10 is critical to hematopoietic cell-fate determination.
- Published
- 2011
24. Isolation and characterization of a bile acid inducible 7α-dehydroxylating operon in Clostridium hylemonae TN271
- Author
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Phillip B. Hylemon, Jason M. Ridlon, and Dae Joong Kang
- Subjects
DNA, Bacterial ,Transcriptional Activation ,Lithocholic acid ,medicine.drug_class ,Operon ,Molecular Sequence Data ,Biology ,Microbiology ,Article ,Bile Acids and Salts ,chemistry.chemical_compound ,Bacterial Proteins ,Chenodeoxycholic acid ,Gene Order ,medicine ,Testosterone ,Enterohepatic circulation ,Conserved Sequence ,Clostridium ,Bile acid ,Deoxycholic acid ,Hydroxysteroid Dehydrogenases ,Cholic acid ,Sequence Analysis, DNA ,Molecular biology ,Infectious Diseases ,Biochemistry ,chemistry ,Genes, Bacterial ,Transcription Initiation Site ,CYP8B1 ,Metabolic Networks and Pathways - Abstract
Primary bile acids are synthesized from cholesterol in the liver, conjugated to either glycine or taurine and secreted into bile. Bile salts undergo enterohepatic circulation several times each day. During this process, they are biotransformed into a variety of metabolites by gut bacteria. The major biotransformation is the 7α-dehydroxylation of cholic acid and chenodeoxycholic acid yielding deoxycholic acid and lithocholic acid, respectively. 7α-Dehydroxylation is a multi-step pathway. The genes encoding enzymes in this pathway have been identified in two species of “high” activity strains of clostridia. Here, we report the isolation and characterization of a bile acid inducible (bai) operon in Clostridium hylemonae , a “low” activity 7α-dehydroxylating strain. The gene organization and sequence of the baiBCDEFGHI operon was highly conserved between C. hylemonae and “high” activity strains. Surprisingly, the baiA gene was missing from the bai operon of C. hylemonae . The baiA gene was isolated using PCR and degenerate oligonucleotide primers. The mRNA start site for the large bai operon was determined and shown to be only 11 bp from the initiation codon of the first gene. It was also discovered that allocholic acid (5α) induced the bai operon and stimulated the conversion of [24- 14 C] cholic acid to [24- 14 C] allodeoxycholic acid in cultures of C. scindens and C. hylemonae allodeoxycholic acid. Finally, it was discovered that the addition of testosterone to the growth medium markedly increased 7α-dehydroxylation of cholic acid in Clostridium scindens and C. hylemonae . We hypothesize that testosterone may be a gratuitous inducer of genes involved in the reductive arm of the bile acid 7α-dehydroxylation pathway.
- Published
- 2010
25. ADAM10 is essential for Notch2-dependent marginal zone B cell development and CD23 cleavage in vivo
- Author
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Daniel H. Conrad, Rania M. El Sayed, Howard C. Crawford, Peter J. Dempsey, Mohey Eldin M. El Shikh, David R. Gibb, Joanna Cichy, Hideo Yagita, Dae Joong Kang, John G. Tew, and Warren J. Rowe
- Subjects
DNA, Complementary ,T-Lymphocytes ,ADAM10 ,Immunology ,Receptors, CCR1 ,Biology ,Polymerase Chain Reaction ,Article ,ADAM10 Protein ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Marginal zone B-cell ,medicine ,Animals ,Immunology and Allergy ,Receptor, Notch2 ,Receptor ,B cell ,030304 developmental biology ,Mice, Knockout ,Recombination, Genetic ,B-Lymphocytes ,0303 health sciences ,Receptors, IgE ,Reverse Transcriptase Polymerase Chain Reaction ,Macrophages ,Gene Amplification ,CD23 ,Membrane Proteins ,Cell Biology ,Exons ,Molecular biology ,ADAM Proteins ,medicine.anatomical_structure ,Knockout mouse ,RNA ,Amyloid Precursor Protein Secretases ,Signal transduction ,Gene Deletion ,Spleen ,Cytokinesis ,030215 immunology - Abstract
The proteolytic activity of a disintegrin and metalloproteinase 10 (ADAM10) regulates cell-fate decisions in Drosophila and mouse embryos. However, in utero lethality of ADAM10−/− mice has prevented examination of ADAM10 cleavage events in lymphocytes. To investigate their role in B cell development, we generated B cell–specific ADAM10 knockout mice. Intriguingly, deletion of ADAM10 prevented development of the entire marginal zone B cell (MZB) lineage. Additionally, cleavage of the low affinity IgE receptor, CD23, was profoundly impaired, but subsequent experiments demonstrated that ADAM10 regulates CD23 cleavage and MZB development by independent mechanisms. Development of MZBs is dependent on Notch2 signaling, which requires proteolysis of the Notch2 receptor by a previously unidentified proteinase. Further experiments revealed that Notch2 signaling is severely impaired in ADAM10-null B cells. Thus, ADAM10 critically regulates MZB development by initiating Notch2 signaling. This study identifies ADAM10 as the in vivo CD23 sheddase and an important regulator of B cell development. Moreover, it has important implications for the treatment of numerous CD23- and Notch-mediated pathologies, ranging from allergy to cancer.
- Published
- 2010
26. Problematizing Lifelong Education Act and exploring alternatives
- Author
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Dae Joong Kang
- Subjects
Political science ,Pedagogy ,Lifelong learning - Abstract
이 글은 평생교육 실천의 토대라 할 수 있는 평생교육법의 한계를 지적하며 재구조화 필요성을 제기한다. 평생교육법은 사회교육법을 계승하면서 평생교육 관련법들의 모법 혹은 기본법으로의 위상을 정립하려는 시도를 해왔으나 기본법의 위상을 가지지 못하고 있다. 평생교육법은 평생교육 개념적으로 표방하는 평생에 걸친 교육을 관장하는 법이 아니라 평생교육기관 조항과 평생교육사 자격 제도를 통해 평생교육이라고 불리는 전문 영역을 구축하는데 기여하고 있다. 연구자는 헌법과 교육기본법에 나타난 평생교육은 국민의 평생에 걸친 교육을 진흥하는 국가의 책무를 나타내는 용어이며, 실천 세계를 규정하는 용어가 될 수 없다고 본다. 연구자는 또 우리나라의 사회교육과 서구의 성인교육 관련 담론이 평생교육을 거쳐 평생학습과 학습사회로 확장되어왔다는 관점에서 평생교육은 학습사회에서 평생학습을 사회적으로 지원하는 제도 혹은 시스템적인 측면을 나타낸다고 본다. 이런 관점에서 ‘평생교육’을 실천 세계를 규정하는 법적인 용어로 사용하는 것은 부적합하므로 이 글에서는 평생교육법을 ‘평생학습진흥법’과 ‘성인계속교육지원법’으로 해체 재구조화할 것을 제안하고 있다.
- Published
- 2009
27. Clostridium scindens baiCD and baiH genes encode stereo-specific 7α/7β-hydroxy-3-oxo-Δ4-cholenoic acid oxidoreductases☆
- Author
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Dae Joong Kang, Phillip B. Hylemon, Doyle Ray Moore, Stephen Barnes, and Jason M. Ridlon
- Subjects
medicine.drug_class ,Operon ,Molecular Sequence Data ,Carboxylic Acids ,Flavoprotein ,Catalysis ,Protein Structure, Secondary ,Article ,Substrate Specificity ,Gene product ,chemistry.chemical_compound ,Oxidoreductase ,Chenodeoxycholic acid ,medicine ,Amino Acid Sequence ,Molecular Biology ,Conserved Sequence ,Clostridium ,chemistry.chemical_classification ,biology ,Bile acid ,Cholic acid ,Stereoisomerism ,Cell Biology ,Molecular biology ,Recombinant Proteins ,Ursodeoxycholic acid ,chemistry ,Biochemistry ,biology.protein ,Chromatography, Thin Layer ,Oxidoreductases ,Sequence Alignment ,medicine.drug - Abstract
Secondary bile acids, formed by intestinal bacteria, are suggested to play a significant role in cancers of the gastrointestinal tract in humans. Bile acid 7alpha/beta-dehydroxylation is carried out by a few species of intestinal clostridia which harbor a multi-gene bile acid inducible (bai) operon. Several genes encoding enzymes in this pathway have been cloned and characterized. However, no gene product(s) has yet been assigned to the production of 3-oxo-Delta4-cholenoic acid intermediates of cholic acid (CA), chenodeoxycholic acid (CDCA) or ursodeoxycholic acid (UDCA). We previously reported that the baiH gene encodes an NADH:flavin oxidoreductase (NADH:FOR); however, the role of this protein in bile acid 7-dehydroxylation is unclear. Homology searches and secondary structural alignments suggest this protein to be similar to flavoproteins which reduce alpha/beta-unsaturated carbonyl compounds. The baiH gene product was expressed in Escherichia coli, purified and discovered to be a stereo-specific NAD(H)-dependent 7beta-hydroxy-3-oxo-Delta4-cholenoic acid oxidoreductase. Additionally, high sequence similarity between the baiH and baiCD gene products suggests the baiCD gene may encode a 3-oxo-Delta4-cholenoic acid oxidoreductase specific for CDCA and CA. We tested this hypothesis using cell extracts prepared from E. coli overexpressing the baiCD gene and discovered that it encodes a stereo-specific NAD(H)-dependent 7alpha-hydroxy-3-oxo-Delta4-cholenoic acid oxidoreductase.
- Published
- 2008
28. Rhizoactivity: Toward a Postmodern Theory of Lifelong Learning
- Author
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Dae Joong Kang
- Subjects
Cooperative learning ,05 social sciences ,Lifelong learning ,050301 education ,050109 social psychology ,Open learning ,Experiential learning ,Learning sciences ,Education ,Epistemology ,Adult education ,Pedagogy ,Active learning ,Learning theory ,0501 psychology and cognitive sciences ,Sociology ,0503 education - Abstract
Although the loss of certainty in the age of postmodernism is questioning knowledge production in general, the emerging discourse of lifelong learning demands a different theory of adult learning in particular. This article aims to offer a conceptual tool for describing learning in adulthood in terms of postmodern and lifelong learning conditions. It approaches the problem from the images of learning and learner that adult education scholarship has produced and identifies that adult learning theory attempts to signify foundational certainty by using binary-trapped adjectives. The author argues that insofar as we continue with the adjective-plus-learning theory, we cannot escape binary thought. The author proposes a new concept, rhizoactivity, to navigate multiplicity of learning in a postmodern world. Anticipated benefits of employing rhizoactivity in understanding learning are discussed in terms of postmodern and lifelong learning conditions.
- Published
- 2007
29. Gut microbiota, cirrhosis, and alcohol regulate bile acid metabolism in the gut
- Author
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Phillip B. Hylemon, Dae Joong Kang, Jasmohan S. Bajaj, and Jason M. Ridlon
- Subjects
Liver Cirrhosis ,Cirrhosis ,Alcohol Drinking ,medicine.drug_class ,Gut flora ,Pharmacology ,digestive system ,Article ,Bile Acids and Salts ,03 medical and health sciences ,Liver disease ,chemistry.chemical_compound ,Feces ,0302 clinical medicine ,medicine ,Humans ,Microbiome ,030304 developmental biology ,0303 health sciences ,Bile acid ,biology ,Ethanol ,business.industry ,Probiotics ,Deoxycholic acid ,Gastroenterology ,General Medicine ,medicine.disease ,biology.organism_classification ,3. Good health ,Gastrointestinal Microbiome ,chemistry ,Biochemistry ,Dysbiosis ,030211 gastroenterology & hepatology ,Farnesoid X receptor ,business ,Signal Transduction - Abstract
The understanding of the complex role of the bile acid-gut microbiome axis in health and disease processes is evolving rapidly. Our focus revolves around the interaction of the gut microbiota with liver diseases, especially cirrhosis. The bile acid pool size has recently been shown to be a function of microbial metabolism of bile acid, and regulation of the microbiota by bile acids is important in the development and progression of several liver diseases. Humans produce a large, conjugated hydrophilic bile acid pool, maintained through positive-feedback antagonism of farnesoid X receptor (FXR) in the intestine and liver. Microbes use bile acids, and via FXR signaling this results in a smaller, unconjugated hydrophobic bile acid pool. This equilibrium is critical to maintain health. The challenge is to examine the manifold functions of gut bile acids as modulators of antibiotic, probiotic, and disease progression in cirrhosis, metabolic syndrome, and alcohol use. Recent studies have shown potential mechanisms explaining how perturbations in the microbiome affect bile acid pool size and composition. With advancing liver disease and cirrhosis, there is dysbiosis in the fecal, ileal, and colonic mucosa, in addition to a decrease in bile acid concentration in the intestine due to the liver problems. This results in a dramatic shift toward the Firmicutes, particularly Clostridium cluster XIVa, and increasing production of deoxycholic acid. Alcohol intake speeds up these processes in the subjects with and without cirrhosis without significant FXR feedback. Taken together, these pathways can impact intestinal and systemic inflammation while worsening dysbiosis. The interaction between bile acids, alcohol, cirrhosis, and dysbiosis is an important relationship that influences intestinal and systemic inflammation, which in turn determines progression of the overall disease process. These interactions and the impact of commonly used therapies for liver disease can provide insight into the pathogenesis of inflammation in humans.
- Published
- 2015
30. Lifelong learning and life history
- Author
-
Dae Joong Kang
- Subjects
Medical education ,Lifelong learning ,Life history ,Psychology - Published
- 2015
31. Bile salt biotransformations by human intestinal bacteria
- Author
-
Phillip B. Hylemon, Jason M. Ridlon, and Dae Joong Kang
- Subjects
Models, Molecular ,medicine.drug_class ,Taurine ,Molecular Sequence Data ,Microbial metabolism ,QD415-436 ,Biology ,Biochemistry ,Microbiology ,Amidohydrolases ,Bile Acids and Salts ,chemistry.chemical_compound ,Endocrinology ,medicine ,Humans ,Amino Acid Sequence ,Hydrogen Sulfide ,Intestinal Mucosa ,Enterohepatic circulation ,Biotransformation ,chemistry.chemical_classification ,bile acids ,Bile acid ,Bacteria ,Molecular Structure ,Sequence Homology, Amino Acid ,Deoxycholic acid ,Hydroxysteroid Dehydrogenases ,Cholic Acids ,Cell Biology ,biology.organism_classification ,Intestines ,Enzyme ,chemistry ,colon cancer ,deoxycholic acid ,Colonic Neoplasms ,7α-dehydroxylation ,gallstone disease ,bile salt hydrolase ,Anaerobic bacteria ,CYP8B1 - Abstract
Secondary bile acids, produced solely by intestinal bacteria, can accumulate to high levels in the enterohepatic circulation of some individuals and may contribute to the pathogenesis of colon cancer, gallstones, and other gastrointestinal (GI) diseases. Bile salt hydrolysis and hydroxy group dehydrogenation reactions are carried out by a broad spectrum of intestinal anaerobic bacteria, whereas bile acid 7-dehydroxylation appears restricted to a limited number of intestinal anaerobes representing a small fraction of the total colonic flora. Microbial enzymes modifying bile salts differ between species with respect to pH optima, enzyme kinetics, substrate specificity, cellular location, and possibly physiological function. Crystallization, site-directed mutagenesis, and comparisons of protein secondary structure have provided insight into the mechanisms of several bile acid-biotransforming enzymatic reactions. Molecular cloning of genes encoding bile salt-modifying enzymes has facilitated the understanding of the genetic organization of these pathways and is a means of developing probes for the detection of bile salt-modifying bacteria. The potential exists for altering the bile acid pool by targeting key enzymes in the 7alpha/beta-dehydroxylation pathway through the development of pharmaceuticals or sequestering bile acids biologically in probiotic bacteria, which may result in their effective removal from the host after excretion.
- Published
- 2006
32. Book Review: Adult Education and Adult Learning
- Author
-
Dae Joong Kang
- Subjects
Adult education ,Transformative learning ,Pedagogy ,Psychology ,Competence (human resources) ,Adult Learning ,Education ,Developmental psychology - Published
- 2006
33. MUSEUM AS A (DE)COLONIZING AGENCY AND PARTICIPATORY LEARNING SPACE: SOUTH KOREAN EXPERIENCE.
- Author
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Hong Lee, Dae Joong Kang, and Seungeun Kim
- Subjects
KOREAN history ,ADULT learning ,HISTORICAL museums ,PUBLIC spaces ,ADULT education ,JAPANESE history - Abstract
Copyright of Canadian Journal for the Study of Adult Education is the property of Canadian Journal for the Study of Adult Education and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
- Published
- 2019
34. Detection of the steroidogenic acute regulatory protein, StAR, in human liver cells
- Author
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William M. Pandak, Kaye Redford, Elizabeth Hall, Dae Joong Kang, Dalila Marques, Daniel Rodriguez-Agudo, Phillip B. Hylemon, Shunlin Ren, and Gregorio Gil
- Subjects
endocrine system ,medicine.medical_specialty ,medicine.drug_class ,Blotting, Western ,Mitochondrion ,Biology ,Cholesterol 7 alpha-hydroxylase ,Cell Line ,Bile Acids and Salts ,Mitochondrial Proteins ,chemistry.chemical_compound ,Internal medicine ,CYP27A1 ,medicine ,Humans ,Electrophoresis, Gel, Two-Dimensional ,RNA, Messenger ,Molecular Biology ,Bile acid ,Cholesterol ,Steroidogenic acute regulatory protein ,Cell Biology ,Phosphoproteins ,Molecular biology ,Hydroxycholesterols ,Recombinant Proteins ,Endocrinology ,Liver ,chemistry ,Cell culture ,Steroid Hydroxylases ,Hepatocytes ,Cholestanetriol 26-Monooxygenase ,Intracellular - Abstract
Overexpressing StAR (a mitochondrial cholesterol transporter) increases (>5-fold) the rate of 27-hydroxylation of cholesterol and the rates of bile acid synthesis in primary rat hepatocytes; suggesting that the transport of cholesterol into mitochondria is rate-limiting for bile acid biosynthesis via the CYP27A1 initiated ‘acidic’ pathway. Our objective was to determine the level of StAR expression in human liver and whether changes in StAR would correlate with changes in CYP27A1 activity/bile acid synthesis rates in human liver tissues. StAR mRNA and protein were detected in primary human hepatocytes and HepG2 cells by RT-PCR/Northern analysis and by Western analysis, respectively. In immunocompetition assays, liver StAR was competed away with the addition of purified human adrenal StAR. Overexpressing CYP27A1 in both cell types led to >2-fold increases in liver StAR concentration. StAR protein levels also increased ∼2-fold with the addition of 27-hydroxycholesterol to HepG2 cell culture medium. Overexpressing StAR increased the rates of 27-hydroxylation of cholesterol/bile acid synthesis in both cell lines and increased intracellular levels of 27-hydroxycholesterol. In conclusion, human liver cells contain regulable StAR protein whose level of expression appears capable of regulating cellular cholesterol homeostasis, representing a potential therapeutic target in the management of hyperlipidemia.
- Published
- 2005
35. Interaction of Prevotella intermedia Strain 17 Leucine-Rich Repeat Domain Protein AdpF with Eukaryotic Cells Promotes Bacterial Internalization
- Author
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Dae-Joong Kang, Tiana Wyant, Dipanwita Sengupta, Cecilia Anaya-Bergman, Janina P. Lewis, Hiroshi Miyazaki, and Arnab K. Ghosh
- Subjects
media_common.quotation_subject ,Immunology ,Protein domain ,Leucine-rich repeat ,Microfilament ,Leucine-Rich Repeat Proteins ,Microbiology ,Prevotella intermedia ,chemistry.chemical_compound ,Bacterial Proteins ,Humans ,Cytochalasin ,Internalization ,media_common ,Analysis of Variance ,Cellular Microbiology: Pathogen-Host Cell Molecular Interactions ,biology ,Proteins ,Gene Expression Regulation, Bacterial ,Fibroblasts ,biology.organism_classification ,Molecular biology ,Cell biology ,Fibronectins ,Nocodazole ,stomatognathic diseases ,Infectious Diseases ,Eukaryotic Cells ,chemistry ,Cell culture ,Parasitology ,HeLa Cells - Abstract
Prevotella intermedia is an oral bacterium implicated in a variety of oral diseases. Although internalization of this bacterium by nonphagocytic host cells is well established, the molecular players mediating the process are not well known. Here, the properties of a leucine-rich repeat (LRR) domain protein, designated AdpF, are described. This protein contains a leucine-rich region composed of 663 amino acid residues, and molecular modeling shows that it folds into a classical curved solenoid structure. The cell surface localization of recombinant AdpF (rAdpF) was confirmed by electron and confocal microscopy analyses. The recombinant form of this protein bound fibronectin in a dose-dependent manner. Furthermore, the protein was internalized by host cells, with the majority of the process accomplished within 30 min. The internalization of rAdpF was inhibited by nystatin, cytochalasin, latrunculin, nocodazole, and wortmannin, indicating that microtubules, microfilaments, and signal transduction are required for the invasion. It is noteworthy that preincubation of eukaryotic cells with AdpF increased P. intermedia 17 internalization by 5- and 10-fold for HeLa and NIH 3T3 fibroblast cell lines, respectively. The addition of the rAdpF protein was also very effective in inducing bacterial internalization into the oral epithelial cell line HN4, as well as into primary cells, including human oral keratinocytes (HOKs) and human umbilical vein endothelial cells (HUVECs). Finally, cells exposed to P. intermedia 17 internalized the bacteria more readily upon reinfection. Taken together, our data demonstrate that rAdpF plays a role in the internalization of P. intermedia 17 by a variety of host cells.
- Published
- 2014
36. Bile Acids and the Gut Microbiome
- Author
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Phillip B. Hylemon, Dae Joong Kang, Jason M. Ridlon, and Jasmohan S. Bajaj
- Subjects
Bile acid ,Extramural ,medicine.drug_class ,Microbiota ,digestive, oral, and skin physiology ,Liver Neoplasms ,Gastroenterology ,Biology ,digestive system ,Gut microbiome ,Article ,Bile Acids and Salts ,Intestines ,Cell Transformation, Neoplastic ,Biochemistry ,medicine ,Humans ,Microbiome ,Bile salt hydrolase ,Intestinal Mucosa ,Cholesterol 7-alpha-Hydroxylase - Abstract
We examine the latest research on the emerging bile acid-gut microbiome axis and its role in health and disease. Our focus revolves around two key microbial pathways for degrading bile salts, and the impact of bile acid composition in the gut on the gut microbiome and host physiology.Bile acid pool size has recently been shown to be a function of microbial metabolism of bile acids in the intestines. Recent studies have shown potential mechanisms explaining how perturbations in the microbiome affect bile acid pool size and composition. Bile acids are emerging as regulators of the gut microbiome at the highest taxonomic levels. The role of bile acids as hormones and potentiators of liver cancer is also emerging.The host and microbiome appear to regulate bile acid pool size. The host produces a large, conjugated hydrophilic bile acid pool, maintained through positive-feedback antagonism of farnesoid X receptor (FXR) in intestine and liver. Members of the microbiome utilize bile acids and their conjugates resulting in agonism of FXR in intestine and liver resulting in a smaller, unconjugated hydrophobic bile acid pool. Hydrophilicity of the bile acid pool is associated with disease states. Reduced bile acid levels in the gut are associated with bacterial overgrowth and inflammation. Diet, antibiotic therapy, and disease states affect the balance of the microbiome-bile acid pool.
- Published
- 2014
37. Colonic inflammation and secondary bile acids in alcoholic cirrhosis
- Author
-
Michael Fuchs, Jasmohan S. Bajaj, Genta Kakiyama, Jason M. Ridlon, Phillip B. Hylemon, Hiroshi Nittono, Douglas M. Heuman, Dae Joong Kang, Emily C. Gurley, Huiping Zhou, Yun Wang, Patrick M. Gillevet, Runping Liu, Arun J. Sanyal, William M. Pandak, and Hajime Takei
- Subjects
Liver Cirrhosis ,Alcoholic liver disease ,medicine.medical_specialty ,Cirrhosis ,Physiology ,Alcohol abuse ,Ileum ,Inflammation ,Gut flora ,Gastroenterology ,Proinflammatory cytokine ,Bile Acids and Salts ,Colonic Diseases ,Feces ,Physiology (medical) ,Internal medicine ,medicine ,Humans ,Hepatology ,biology ,Middle Aged ,medicine.disease ,biology.organism_classification ,Alcoholism ,medicine.anatomical_structure ,Call for Papers ,medicine.symptom - Abstract
Alcohol abuse with/without cirrhosis is associated with an impaired gut barrier and inflammation. Gut microbiota can transform primary bile acids (BA) to secondary BAs, which can adversely impact the gut barrier. The purpose of this study was to define the effect of active alcohol intake on fecal BA levels and ileal and colonic inflammation in cirrhosis. Five age-matched groups {two noncirrhotic (control and drinkers) and three cirrhotic [nondrinkers/nonalcoholics (NAlc), abstinent alcoholic for >3 mo (AbsAlc), currently drinking (CurrAlc)]} were included. Fecal and serum BA analysis, serum endotoxin, and stool microbiota using pyrosequencing were performed. A subgroup of controls, NAlc, and CurrAlc underwent ileal and sigmoid colonic biopsies on which mRNA expression of TNF-α, IL-1β, IL-6, and cyclooxygenase-2 (Cox-2) were performed. One hundred three patients (19 healthy, 6 noncirrhotic drinkers, 10 CurrAlc, 38 AbsAlc, and 30 NAlc, age 56 yr, median MELD: 10.5) were included. Five each of healthy, CurrAlc, and NAlc underwent ileal/colonic biopsies. Endotoxin, serum-conjugated DCA and stool total BAs, and secondary-to-primary BA ratios were highest in current drinkers. On biopsies, a significantly higher mRNA expression of TNF-α, IL-1β, IL-6, and Cox-2 in colon but not ileum was seen in CurrAlc compared with NAlc and controls. Active alcohol use in cirrhosis is associated with a significant increase in the secondary BA formation compared with abstinent alcoholic cirrhotics and nonalcoholic cirrhotics. This increase in secondary BAs is associated with a significant increase in expression of inflammatory cytokines in colonic mucosa but not ileal mucosa, which may contribute to alcohol-induced gut barrier injury.
- Published
- 2014
38. Fecal transplant to mitigate hyperammonemia and hepatic encephalopathy in animal models
- Author
-
Phillip B. Hylemon, Jasmohan S. Bajaj, and Dae Joong Kang
- Subjects
Gastrointestinal tract ,Hepatology ,biology ,business.industry ,medicine.drug_class ,Gastrointestinal Microbiome ,Antibiotics ,Specialties of internal medicine ,Hyperammonemia ,General Medicine ,Gut flora ,biology.organism_classification ,medicine.disease ,RC581-951 ,Immunology ,medicine ,Microbiome ,business ,Hepatic encephalopathy ,Feces - Abstract
After treatment of mice with oral antibioticsand PEG to deplete indigenous bacteria, mice wereinoculated with a consortium of 8 bacteria with lowurease gene content. This new gut microbiota wasrelatively stable for up to 120 days. The establishedof a new gut microbiota with less urease activitywas associated with decreased morbidity and mor-tality of a liver injury mouse model. Interestingly,no adverse effects on the mice body weight or mor-tality for over 1 year after fecal microbiota trans-plant (FMT) was noted. However, perturbations ofthe microbiome by antibiotics can select for bacteri-al resistance. Nevertheless, FMT, which introducesa healthy bacterial community into selected pa-tients, has great promise to treat diseases related tothe microbiome that are otherwise difficult to treat.This has been used for
- Published
- 2015
39. Reply
- Author
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Huiping Zhou, Bajaj Js, Dae Joong Kang, and Hylemon Pb
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Hepatology ,business.industry ,Immunology ,medicine ,medicine.symptom ,Systemic inflammation ,medicine.disease ,business ,Chronic periodontitis - Published
- 2015
40. O090 : Humanization of germ-free mice with alcoholic cirrhotic microbiota, but not healthy microbiota, induces bacterial translocation and a pro-inflammatory milieu, which is ameliorated with lactobacillus GG
- Author
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Phillip B. Hylemon, Oliver Fiehn, Jasmohan S. Bajaj, D. Grapov, William M. Pandak, Jason M. Ridlon, Ryan Balfour Sartor, Douglas M. Heuman, Patrick M. Gillevet, Genta Kakiyama, and Dae Joong Kang
- Subjects
Lactobacillus GG ,Hepatology ,Germ ,Bacterial translocation ,Biology ,Microbiology - Published
- 2015
41. ADAM10 regulates transcription factor expression required for plasma cell function
- Author
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Daniel H. Conrad, Dae-Joong Kang, Lee Dean, and Natalia S. Chaimowitz
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B Cells ,Immunofluorescence ,lcsh:Medicine ,Cell Count ,Cell Separation ,Plasma cell ,ADAM10 Protein ,Mice ,Lymphoid Organs ,lcsh:Science ,Immune Response ,Regulation of gene expression ,Multidisciplinary ,DNA-Binding Proteins ,medicine.anatomical_structure ,Proto-Oncogene Proteins c-bcl-6 ,Medicine ,Immunohistochemical Analysis ,Research Article ,XBP1 ,Immune Cells ,Plasma Cells ,Immunology ,Immunoglobulins ,Biology ,Bacterial Proteins ,PRDM1 ,medicine ,Extracellular ,Animals ,Antibody-Producing Cells ,Transcription factor ,B cell ,Integrases ,lcsh:R ,Germinal center ,Membrane Proteins ,Germinal Center ,Molecular biology ,ADAM Proteins ,Luminescent Proteins ,Gene Expression Regulation ,Immunoglobulin G ,Immune System ,Antibody Formation ,Immunologic Techniques ,Clinical Immunology ,lcsh:Q ,Amyloid Precursor Protein Secretases ,Immunologic Memory ,Transcription Factors - Abstract
A disintegrin and metalloprotease 10 (ADAM10) is a key regulator of cellular processes by shedding extracellular domains of transmembrane proteins. We have previously demonstrated that deletion of B cell expressed ADAM10 results in changes in lymphoid tissue architecture and impaired germinal center (GC) formation. In this study, mice were generated in which ADAM10 is deleted in B cells following class switch recombination (ADAM10(Δ/Δ)IgG1-cre(+/-) mice). Despite normal GC formation, antibody responses were impaired in ADAM10(Δ/Δ)IgG1-cre(+/-) mice, implicating ADAM10 in post-GC and extrafollicular B cell terminal differentiation. Surprisingly, plasma cell (PC) numbers were normal in ADAM10(Δ/Δ)IgG1-cre(+/-) mice when compared to controls. However, PCs isolated from ADAM10(Δ/Δ)IgG1-cre(+/-) mice exhibited decreased expression of transcription factors important for PC function: Prdm1, Xbp1 and Irf4. Bcl6 is a GC transcriptional repressor that inhibits the PC transcriptional program and thus must be downregulated for PC differentiation to occur. Bcl6 expression was increased in PCs isolated from ADAM10(Δ/Δ)IgG1-cre(+/-) mice at both the mRNA and protein level. These results demonstrate that ADAM10 is required for proper transcription factor expression in PCs and thus, for normal PC function.
- Published
- 2012
42. B cell development (WS-030)
- Author
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M. Pruitt, Dae-Joong Kang, Maki Touma, D. Gatto, Wendy Dubois, Z. Herincs, R. M. El Sayed, Shuling Zhang, Hideo Yagita, Joanna Cichy, Kento Minamino, Peter J. Dempsey, P. Pam Schwartzberg, Julie A. Readinger, H. Singh, T. Vu, David R. Gibb, L. Lu, Gábor Koncz, D. Szili, A. Funnell, Harry D. Bear, Shinsuke Taki, Lino Tessarollo, John G. Tew, Takumi Adachi, A. Hancz, Melinda G. Simon, Gabriella Sármay, Koji Nagaoka, Kayo Inaba, Robert Brink, Howard C. Crawford, Ellis L. Reinherz, Kyoko Ochiai, M.E. El Shikh, Richard C. Robinson, Julie Wu, M. Yang, Kazuhiko Takahara, R. Pearson, Linda K. Clayton, Masoud H. Manjili, Daniel H. Conrad, Derin B. Keskin, M. Crossley, Beverly A. Mock, and S. Saleem
- Subjects
medicine.anatomical_structure ,Immunology ,medicine ,Immunology and Allergy ,General Medicine ,Anatomy ,Biology ,Gray (horse) ,B cell - Published
- 2010
43. ADAM10 regulates B cell development and immunoglobulin production (138.6)
- Author
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David R Gibb, Mohey El Shikh, Dae-Joong Kang, Rania El Sayed, Howard Crawford, John G Tew, and Daniel H Conrad
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Immunology ,Immunology and Allergy - Abstract
Members of the disintegrin and metalloprotease (ADAM) family can regulate lymphocyte development and function by cleaving membrane receptors. Previous studies showed that ADAM10 cleaves the B cell receptors, CD23 and Notch2, in vitro. However, in the absence of in vivo models, the physiologic impact of these events has not been examined. Thus, we generated B cell-specific ADAM10 KO and transgenic (Tg) mice to determine the role of ADAM10 in B cell development and function. Notch signaling regulates the differentiation of common lymphoid progenitors (CLPs) by promoting T cell fate. Accordingly, overexpression of ADAM10 in CLPs completely blocked B cell development. Deletion of ADAM10 from B cells in ADAM10fl/fl, CD19-cre+ mice prevented differentiation of marginal zone B cells, which is dependent on Notch2 signaling. In addition, expression of CD23 on ADAM10null B cells was dramatically elevated while levels of soluble CD23 were reduced in serum. As a result, IgE production by ADAM10fl/fl, CD19-cre+ mice was remarkably suppressed upon immunization, mimicking the response of CD23Tg mice. Finally, production of IgG1 and IgG2b was profoundly inhibited, suggesting a novel role for ADAM10 in class-switching to IgG. These results illustrate the physiologic role of ADAM10 in Notch signaling and CD23 cleavage. Moreover, they identify ADAM10 as a critical regulator of B cell development and immunoglobulin production. AHA 0815066E, NIAID R01AI18697, NIAID U19AI077435
- Published
- 2009
44. ADAM-10 Overexpression Inhibits B cell Development and Promotes Myeloid-derived Suppressor Cell Granulopoesis
- Author
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Daniel H. Conrad, D.R. Gibb, J. Allen, and Dae-Joong Kang
- Subjects
medicine.anatomical_structure ,Chemistry ,Immunology ,Cancer research ,medicine ,Myeloid-derived Suppressor Cell ,Immunology and Allergy ,B cell - Published
- 2009
45. Colonic inflammation and secondary bile acids in alcoholic cirrhosis.
- Author
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Kakiyama, Genta, Hylemon, Phillip B., Huiping Zhou, Pandak, William M., Heuman, Douglas M., Dae Joong Kang, Hajime Takei, Hiroshi Nittono, Ridlon, Jason M., Fuchs, Michael, Gurley, Emily C., Yun Wang, Runping Liu, Sanyal, Arun J., Gillevet, Patrick M., and Bajaj, Jasmohan S.
- Abstract
Alcohol abuse with/without cirrhosis is associated with an impaired gut barrier and inflammation. Gut microbiota can transform primary bile acids (BA) to secondary BAs, which can adversely impact the gut barrier. The purpose of this study was to define the effect of active alcohol intake on fecal BA levels and ileal and colonic inflammation in cirrhosis. Five age-matched groups {two noncirrhotic (control and drinkers) and three cirrhotic [nondrinkers/nonalcoholics (NAlc), abstinent alcoholic for >3 mo (AbsAlc), currently drinking (CurrAlc)]} were included. Fecal and serum BA analysis, serum endotoxin, and stool microbiota using pyrosequencing were performed. A subgroup of controls, NAlc, and CurrAlc underwent ileal and sigmoid colonic biopsies on which mRNA expression of TNF-α, IL-1β, IL-6, and cyclooxygenase-2 (Cox-2) were performed. One hundred three patients (19 healthy, 6 noncirrhotic drinkers, 10 CurrAlc, 38 AbsAlc, and 30 NAlc, age 56 yr, median MELD: 10.5) were included. Five each of healthy, CurrAlc, and NAlc underwent ileal/colonic biopsies. Endotoxin, serum-conjugated DCA and stool total BAs, and secondary-to-primary BA ratios were highest in current drinkers. On biopsies, a significantly higher mRNA expression of TNFα-, IL-1β, IL-6, and Cox-2 in colon but not ileum was seen in CurrAlc compared with NAlc and controls. Active alcohol use in cirrhosis is associated with a significant increase in the secondary BA formation compared with abstinent alcoholic cirrhotics and nonalcoholic cirrhotics. This increase in secondary BAs is associated with a significant increase in expression of inflammatory cytokines in colonic mucosa but not ileal mucosa, which may contribute to alcohol-induced gut barrier injury. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
46. ADAM10 Regulates Transcription Factor Expression Required for Plasma Cell Function.
- Author
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Chaimowitz, Natalia S., Dae-Joong Kang, Dean, Lee M., Conrad, Daniel H., and Khan, Wasif N.
- Subjects
- *
DISINTEGRINS , *METALLOPROTEINASES , *PROTEINS , *B cells , *LYMPHOID tissue , *GERMINAL centers , *PLASMA cells - Abstract
A disintegrin and metalloprotease 10 (ADAM10) is a key regulator of cellular processes by shedding extracellular domains of transmembrane proteins. We have previously demonstrated that deletion of B cell expressed ADAM10 results in changes in lymphoid tissue architecture and impaired germinal center (GC) formation. In this study, mice were generated in which ADAM10 is deleted in B cells following class switch recombination (ADAM10Δ/ΔIgG1-cre+/- mice). Despite normal GC formation, antibody responses were impaired in ADAM10Δ/ΔIgG1-cre+/- mice, implicating ADAM10 in post-GC and extrafollicular B cell terminal differentiation. Surprisingly, plasma cell (PC) numbers were normal in ADAM10Δ/ΔIgG1- cre+/- mice when compared to controls. However, PCs isolated from ADAM10Δ/ΔIgG1-cre+/- mice exhibited decreased expression of transcription factors important for PC function: Prdm1, Xbp1 and Irf4. Bcl6 is a GC transcriptional repressor that inhibits the PC transcriptional program and thus must be downregulated for PC differentiation to occur. Bcl6 expression was increased in PCs isolated from ADAM10Δ/ΔIgG1-cre+/- mice at both the mRNA and protein level. These results demonstrate that ADAM10 is required for proper transcription factor expression in PCs and thus, for normal PC function. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF
47. Adult Education and Adult Learning.
- Author
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Dae Joong Kang
- Subjects
ADULT education ,NONFICTION - Abstract
The article reviews the book "Adult Education and Adult Learning," by Knud Illeris.
- Published
- 2006
- Full Text
- View/download PDF
48. ADAM10 Overexpression Shifts Lympho- and Myelopoiesis by Dysregulating Site 2/Site 3 Cleavage Products of Notch.
- Author
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Gibb, David R., Saleem, Sheinei J., Dae-Joong Kang, Subler, Mark A., and Conrad, Daniel H.
- Subjects
- *
HEMATOPOIESIS , *LABORATORY mice , *TRANSGENE expression , *T cells , *B cells - Abstract
Although the physiological consequences of Notch signaling in hematopoiesis have been extensively studied, the differential effects of individual notch cleavage products remain to be elucidated. Given that ADAM10 is a critical regulator of Notch and that its deletion is embryonically lethal, we generated mice that overexpress ADAM10 (ADAM10 transgenic [A10Tg]) at early stages of lympho- and myeloid development. Transgene expression resulted in abrogated B cell development, delayed T cell development in the thymus, and unexpected systemic expansion of CD11b+Gr-1+ cells, also known as myeloid-derived suppressor cells. Mixed bone marrow reconstitution assays demonstrated that transgene expression altered hematopoiesis via a cell-intrinsic mechanism. Consistent with previously reported observations, we hypothesized that ADAM10 overexpression dysregulated Notch by uncoupling the highly regulated proteolysis of Notch receptors. This was confirmed using an in vitro model of hematopoiesis via culturing A10Tg hematopoietic Lineage-Sca-1+c-Kit+ cells with OP-9 stromal cells in the presence or absence of Delta-like 1, a primary ligand for Notch. Blockade of the site 2 (S2) and site 3 (S3) cleavage of the Notch receptor demonstrated differential effects on hematopoiesis. OP9-DL1 cultures containing the ADAM10 inhibitor (S2 cleavage site) enhanced and rescued B cell development from wild-type and A10Tg Lineage-Sca-1+c-Kit+ cells, respectively. In contrast, blockade of γ-secretase at the S3 cleavage site induced accumulation of the S2 product and consequently prevented B cell development and resulted in myeloid cell accumulation. Collectively, these findings indicate that the differential cleavage of Notch into S2 and S3 products regulated by ADAM10 is critical to hematopoietic cell-fate determination. [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
- View/download PDF
49. Bile salt biotransformations by human intestinal bacteria
- Author
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Jason M. Ridlon, Dae-Joong Kang, and Phillip B. Hylemon
- Subjects
bile acids ,deoxycholic acid ,7α-dehydroxylation ,gallstone disease ,colon cancer ,bile salt hydrolase ,Biochemistry ,QD415-436 - Abstract
Secondary bile acids, produced solely by intestinal bacteria, can accumulate to high levels in the enterohepatic circulation of some individuals and may contribute to the pathogenesis of colon cancer, gallstones, and other gastrointestinal (GI) diseases. Bile salt hydrolysis and hydroxy group dehydrogenation reactions are carried out by a broad spectrum of intestinal anaerobic bacteria, whereas bile acid 7-dehydroxylation appears restricted to a limited number of intestinal anaerobes representing a small fraction of the total colonic flora. Microbial enzymes modifying bile salts differ between species with respect to pH optima, enzyme kinetics, substrate specificity, cellular location, and possibly physiological function. Crystallization, site-directed mutagenesis, and comparisons of protein secondary structure have provided insight into the mechanisms of several bile acid-biotransforming enzymatic reactions. Molecular cloning of genes encoding bile salt-modifying enzymes has facilitated the understanding of the genetic organization of these pathways and is a means of developing probes for the detection of bile salt-modifying bacteria. The potential exists for altering the bile acid pool by targeting key enzymes in the 7α/β-dehydroxylation pathway through the development of pharmaceuticals or sequestering bile acids biologically in probiotic bacteria, which may result in their effective removal from the host after excretion.
- Published
- 2006
- Full Text
- View/download PDF
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