• Title/Summary/Keyword: human life

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HIF-1-Dependent Induction of Jumonji Domain-Containing Protein (JMJD) 3 under Hypoxic Conditions

  • Lee, Ho-Youl;Choi, Kang;Oh, Hookeun;Park, Young-Kwon;Park, Hyunsung
    • Molecules and Cells
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    • v.37 no.1
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    • pp.43-50
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    • 2014
  • Jumonji domain-containing proteins (JMJD) catalyze the oxidative demethylation of a methylated lysine residue of histones by using $O_2$, ${\alpha}$-ketoglutarate, vitamin C, and Fe(II). Several JMJDs are induced by hypoxic stress to compensate their presumed reduction in catalytic activity under hypoxia. In this study, we showed that an H3K27me3 specific histone demethylase, JMJD3 was induced by hypoxia-inducible factor (HIF)-$1{\alpha}/{\beta}$ under hypoxia and that treatment with Clioquinol, a HIF-$1{\alpha}$ activator, increased JMJD3 expression even under normoxia. Chromatin immunoprecipitation (ChIP) analyses showed that both HIF-$1{\alpha}$ and its dimerization partner HIF-$1{\beta}$/Arnt occupied the first intron region of the mouse JMJD3 gene, whereas the HIF-$1{\alpha}/{\beta}$ heterodimer bound to the upstream region of the human JMJD3, indicating that human and mouse JMJD3 have hypoxia-responsive regulatory regions in different locations. This study shows that both mouse and human JMJD3 are induced by HIF-1.

Structural Study of Monomethyl Fumarate-Bound Human GAPDH

  • Park, Jun Bae;Park, Hayeong;Son, Jimin;Ha, Sang-Jun;Cho, Hyun-Soo
    • Molecules and Cells
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    • v.42 no.8
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    • pp.597-603
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    • 2019
  • Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a core enzyme of the aerobic glycolytic pathway with versatile functions and is associated with cancer development. Recently, Kornberg et al. published the detailed correlation between GAPDH and di- or monomethyl fumarate (DMF or MMF), which are well-known GAPDH antagonists in the immune system. As an extension, herein, we report the crystal structure of MMF-bound human GAPDH at $2.29{\AA}$. The MMF molecule is covalently linked to the catalytic Cys152 of human GAPDH, and inhibits the catalytic activity of the residue and dramatically reduces the enzymatic activity of GAPDH. Structural comparisons between $NAD^+$-bound GAPDH and MMF-bound GAPDH revealed that the covalently linked MMF can block the binding of the $NAD^+$ cosubstrate due to steric hindrance of the nicotinamide portion of the $NAD^+$ molecule, illuminating the specific mechanism by which MMF inhibits GAPDH. Our data provide insights into GAPDH antagonist development for GAPDH-mediated disease treatment.

Purification, crystallization and X-ray diffraction of heparan sulfate bounded human RAGE

  • Park, Jun bae;Yoo, Youngki;Ong, Belinda Xiang Yu;Kim, Juyeon;Cho, Hyun-Soo
    • Biodesign
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    • v.5 no.3
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    • pp.122-125
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    • 2017
  • Receptor for advanced glycation end products (RAGE) is one of the single transmembrane domain containing receptors and causes various inflammatory diseases including diabetes and atherosclerosis. RAGE extracellular domain has three consecutive IgG-like domains (V-C1-C2 domain) which interact with various soluble ligands including heparan sulfate or HMGB1. Studies have shown that each ligand induces different oligomeric forms of RAGE which results in a ligand-specific signal transduction. The structure of mouse RAGE bound to heparan sulfate has been previously determined but the electron density map of heparan sulfate was too ambiguous that the exact position of heparin sulfate could not be defined. Furthermore, the complex structure of human RAGE and heparin sulfate still remains elusive. Therefore, to determine the structure, human RAGE was overexpressed using bacterial expression system and crystallized using the sitting drop method in the condition of 0.1 M sodium acetate trihydrate pH 4.6, 8 % (w/v) polyethylene glycol 4,000 at 290 K. The crystal diffracted to 3.6 Å resolution and the space group is C121 with unit cell parameters a= 206.04 Å, b= 68.64 Å, c= 98.73 Å, α= 90.00°, β= 90.62°, γ= 90.00°.

A Study of the Theoretical Ethics Approach to Bioethics - Based on the ethics of Singer, Kant, and Aristotle - (생명윤리에 대한 이론 윤리학 탐구 - 싱어, 칸트, 아리스토텔레스 윤리학을 중심으로 -)

  • Kwak, Young-kuen
    • Journal of Korean Philosophical Society
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    • v.146
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    • pp.1-24
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    • 2018
  • The purpose of this paper is to explore the meaning of theoretical ethics regarding bioethics. First, I explore the meanings and limitations of the bioethics domain for 'the principle of equal consideration of interests' and the 'preference utilitarianism' concepts Singer presents. Secondly, I emphasize the significance of Kant's ethics in the domain of bioethics. Lastly, I suggest that Aristotle's virtue ethics should be realized in the domain of bioethics. Furthermore, I would like to suggest the meaning of human life through this. Singer's argument brings up a new topic about the meaning of evolved life not considered in the history of traditional ethics. He presented undeniable opinions about human dignity that he took for granted. In addition, it is assessed that the scope extension for the life respect target has been reasonably achieved. Contrary to this, Kant's ethics explains the meaning of human dignity based on its metaphysical meaning. Furthermore, it provides an appropriate orientation for human life. Embracing their claims is not sufficient to explain the meaning of Good Life. The meaning of Good Life is likely to be resolved through the application of Aristotle's virtue ethics. The meaning of a being of substance is living and furthermore, it is inherent to being itself.

A Producing Process for Korean Nursing Knowledge and Discourse on Analytic Prospects (한국 간호지식체의 생산과정과 담론분석적 전망)

  • 권봉숙;박형숙
    • Journal of Korean Academy of Nursing
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    • v.27 no.1
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    • pp.61-70
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    • 1997
  • The purpose of this study was to identify the producing process for Korean nursing knowledge as applied by Foucault's discourse analytic method. By Foucault's discourse analytic method, the problem is not what is knowledge but what sort of knowledge is made up through specific level of practice. A Korean body of nursing knowledge has been discussed since 1980. At the end of 19th century, missionaries transplanted western nursing knowledge and method to Korea. Western nursing knowledge and methods have been developed continuously with both merits and demerits to Korean society. Recently our world has be come a global community via advances in transportation and correspondence. Although each person is different in skin color and shape. there is a clear line between Oriental people and Western people. Nursing science is only one in our world. but western humanistic nursing practice based on western worldview and human life has limits. It is natural that the Koreans as Oriental people have a systemic nursing science to reveal the specific experiential and concrete body of nursing knowledge rooted in the Korean worldview and human life. Nursing science is to understand human beings, to promote health. to prevent illness. to restore health. to alleviate suffering and to search for principles needed throughout all of human life. In Korea, now is the quickening period to shape a Korean body of nursing knowledge because of a shortage of nursing language in matters of intellectual recognition, and unfamiliar practical nursing field where there is no familiarity in the system of nursing research methodology. In reviewing articles from the Journal of the Nurses' Academic Society on Korean body of nursing knowledge, it was found that there are two common features. The first, human body and mind are inseperable that is one unit in this world and health is keeping a harmonious relationship between human body and mind. The second, Korean nursing practice is based on human nature and family ties. Accordingly discourse analysis has a good future prospect to produce a Korean body of nursing knowledge for analytic research on body and mind monism and family centered care based on human nature and family ties.

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