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RUNX1 Upregulation Causes Mitochondrial Dysfunction via Regulating the PI3K-Akt Pathway in iPSC from Patients with Down Syndrome

  • Yanna Liu;Yuehua Zhang;Zhaorui Ren;Fanyi Zeng;Jingbin Yan
    • Molecules and Cells
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    • v.46 no.4
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    • pp.219-230
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    • 2023
  • Down syndrome (DS) is the most common autosomal aneuploidy caused by trisomy of chromosome 21. Previous studies demonstrated that DS affected mitochondrial functions, which may be associated with the abnormal development of the nervous system in patients with DS. Runt-related transcription factor 1 (RUNX1) is an encoding gene located on chromosome 21. It has been reported that RUNX1 may affect cell apoptosis via the mitochondrial pathway. The present study investigated whether RUNX1 plays a critical role in mitochondrial dysfunction in DS and explored the mechanism by which RUNX1 affects mitochondrial functions. Expression of RUNX1 was detected in induced pluripotent stem cells of patients with DS (DS-iPSCs) and normal iPSCs (N-iPSCs), and the mitochondrial functions were investigated in the current study. Subsequently, RUNX1 was overexpressed in N-iPSCs and inhibited in DS-iPSCs. The mitochondrial functions were investigated thoroughly, including reactive oxygen species levels, mitochondrial membrane potential, ATP content, and lysosomal activity. Finally, RNA-sequencing was used to explore the global expression pattern. It was observed that the expression levels of RUNX1 in DS-iPSCs were significantly higher than those in normal controls. Impaired mitochondrial functions were observed in DS-iPSCs. Of note, overexpression of RUNX1 in N-iPSCs resulted in mitochondrial dysfunction, while inhibition of RUNX1 expression could improve the mitochondrial function in DS-iPSCs. Global gene expression analysis indicated that overexpression of RUNX1 may promote the induction of apoptosis in DS-iPSCs by activating the PI3K/Akt signaling pathway. The present findings indicate that abnormal expression of RUNX1 may play a critical role in mitochondrial dysfunction in DS-iPSCs.

Effects of a Strength Based I-Change Smoking Cessation Program for Smoking Middle School Boys (강점기반 I-Change 금연프로그램이 흡연남자중학생의 금연에 미치는 효과)

  • Kim, Jung Hee;Choi, Yeon Hee
    • Journal of Korean Academy of Nursing
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    • v.47 no.2
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    • pp.164-177
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    • 2017
  • Purpose: This study was done to develop a strength based I-change smoking cessation program for middle school boys and identified its effects. Methods: The study design was a nonequivalent control group pre-post test design. The participants were 97 middle school students from D city, who were in school from April 6 to September 25, 2015. The experimental group participated in the strength based I-change smoking cessation program, while the comparative group participated in a general smoking cessation program. The control group did not participate in any program. Data analyses involved $x^2$-test, Fishers' exact test, Bonferroni test, and Repeated measures ANOVA, with the IBM SPSS for Windows (version 20.0) program. Results: Compared to the comparison and control groups, the experimental group showed significant improvement in knowledge, attitude, self-efficacy, behavior change. Also cotinine in urine and modeling of social influence in the experimental group significantly decreased after the strength based I-change smoking cessation program. Conclusion: These findings indicate that the strength based I-change smoking cessation program is an effective intervention for middle school boys who smoke. The findings suggest that such programs can be used at public health centers or through school health education to decrease smoking in adolescents.

Delayed-constrained scheduling for a game server virtual machine (게임서버 가상머신을 위한 지연 제약 스케줄링)

  • kang, Kiwook;Ko, Cherl-hong;Hong, Jiman;Paik, Doowon
    • Journal of Korea Game Society
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    • v.16 no.4
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    • pp.57-68
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    • 2016
  • As the size of the data used in the game application increase gradually, the physical resources of game server grow. Accordingly, it is necessary to/it is required to introduce I/O virtualization in game server to improve I/O performance of the server. But it is difficult to ensure high responsiveness in game server where I/O delay change from time to time. To maximize the benefit of I/O virtualization, guaranteeing I/O response time is very important and it is necessary to have I/O scheduling techniques to manage the I/O latency in the order of priority of virtual machines. In this paper, we propose an efficient delay-constrained scheduling algorithm in a virtualization environment to ensure maximum I/O latency. In addition, a reduced amount of loss of the packet was found to increase the fairness of scheduling in the experiments with the proposed scheme.

Four Voltage-Gated Potassium Currents in Trigeminal Root Ganglion Neurons

  • Choi, Seung Ho;Youn, Chang;Park, Ji-Il;Jeong, Soon-Yeon;Oh, Won-Man;Jung, Ji-Yeon;Kim, Won-Jae
    • International Journal of Oral Biology
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    • v.38 no.1
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    • pp.13-19
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    • 2013
  • Various voltage-gated $K^+$ currents were recently described in dorsal root ganglion (DRG) neurons. However, the characterization and diversity of voltage-gated $K^+$ currents have not been well studied in trigeminal root ganglion (TRG) neurons, which are similar to the DRG neurons in terms of physiological roles and anatomy. This study was aimed to investigate the characteristics and diversity of voltage-gated $K^+$ currents in acutely isolated TRG neurons of rat using whole cell patch clamp techniques. The first type (type I) had a rapid, transient outward current ($I_A$) with the largest current size having a slow inactivation rate and a sustained delayed rectifier outward current ($I_K$) that was small in size having a fast inactivation rate. The $I_A$ currents of this type were mostly blocked by TEA and 4-AP, K channel blockers whereas the $I_K$ current was inhibited by TEA but not by 4-AP. The second type had a large $I_A$ current with a slow inactivation rate and a medium size-sustained delayed $I_K$ current with a slow inactivation rate. In this second type (type II), the sensitivities of the $I_A$ or $I_K$ current by TEA and 4-AP were similar to those of the type I. The third type (type III) had a medium sized $I_A$ current with a fast inactivation rate and a large sustained $I_K$ current with the slow inactivation rate. In type III current, TEA decreased both $I_A$ and $I_K$ but 4-AP only blocked $I_A$ current. The fourth type (type IV) had a smallest $I_A$ with a fast inactivation rate and a large $I_K$ current with a slow inactivation rate. TEA or 4-AP similarly decreased the $I_A$ but the $I_K$ was only blocked by 4-AP. These findings suggest that at least four different voltage-gated $K^+$ currents in biophysical and pharmacological properties exist in the TRG neurons of rats.

Anti-proliferative and Apoptosis Inducing Effect of Momordin I on Oral Carcinoma (KB) Cells

  • Seo, Kyeong-Seong;Kim, Jeong-Hee;Kim, Yeo-Gab
    • International Journal of Oral Biology
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    • v.32 no.3
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    • pp.113-118
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    • 2007
  • Treatment of oral cancers with chemotherapeutic agents become evaluated as an effective method to reduce cancer cell proliferation. Anti-proliferative and anti-oral cancer activities of momordin I on oral cancer cells were evaluated in this study. Momordin I was originally purified from a natural product, Ampelopsis radix and showed the antiproliferative activity against oral carcinoma, KB cells. Obtained $IC_{50}$ value was approximately $10.4{\mu}g/ml$. Time-and dose-dependent chromosomal DNA fragmentations were observed in momordin I-treated KB cells. Flow cytometry analysis showed time-dependent apoptotic cell appearance after treatment of momordin I. Approximately 18.6% apoptotic cells were observed at 72 hours after $20{\mu}g/ml$ of momordin I treatment. These observation were consistent with the results obtained in DNA fragmentation analysis. These data suggest that momordin I has anti-proliferative effect and induces cell death in KB cells through apoptosis.

Association between prehospital i-gel insertion and PCO2 in patients with out-of-hospital cardiac arrest

  • Cho, Eunsom;Cho, Eun-Hye;Kim, Hyuk-Hoon;Choi, Sang-Cheon;Min, Young-Gi;Kang, So Young;Chae, Minjung Kathy
    • Journal of The Korean Society of Emergency Medicine
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    • v.29 no.6
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    • pp.578-584
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    • 2018
  • Objective: This study examined the initial partial pressure of carbon dioxide ($PCO_2$) as a possible indicator of prehospital ventilation and its association with prehospital i-gel in out-of-hospital cardiac arrest (OHCA) patients. Methods: The demographics and arrest parameters, including i-gel insertion and initial arterial blood gas analysis, of OHCA patients who visited the emergency department were analyzed retrospectively. Linear regression analysis was performed to examine the association between i-gel insertion and the initial $PCO_2$. Results: A total of 106 patients were investigated. Fifty-six patients had prehospital i-gel insertion and 50 patients did not have a prehospital advanced airway. The initial $PCO_2$ was higher in the i-gel group than the no advanced airway group (105.2 mmHg [77.5-134.9] vs. 87.5 mmHg [56.8-115.3], P=0.03). Prehospital i-gel insertion was associated with a higher initial $PCO_2$ level (${\beta}$ coefficient, 20.3; 95% confidence interval, 2.6-37.9; P=0.03). Conclusion: Prehospital insertion of i-gel was associated with higher initial $PCO_2$ values in OHCA patients compared to no advanced airway.

The Downregulation of Somatic A-Type $K^+$ Channels Requires the Activation of Synaptic NMDA Receptors in Young Hippocampal Neurons of Rats

  • Kang, Moon-Seok;Yang, Yoon-Sil;Kim, Seon-Hee;Park, Joo-Min;Eun, Su-Yong;Jung, Sung-Cherl
    • The Korean Journal of Physiology and Pharmacology
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    • v.18 no.2
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    • pp.135-141
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    • 2014
  • The downregulation of A-type $K^+$ channels ($I_A$ channels) accompanying enhanced somatic excitability can mediate epileptogenic conditions in mammalian central nervous system. As $I_A$ channels are dominantly targeted by dendritic and postsynaptic processings during synaptic plasticity, it is presumable that they may act as cellular linkers between synaptic responses and somatic processings under various excitable conditions. In the present study, we electrophysiologically tested if the downregulation of somatic $I_A$ channels was sensitive to synaptic activities in young hippocampal neurons. In primarily cultured hippocampal neurons (DIV 6~9), the peak of $I_A$ recorded by a whole-cell patch was significantly reduced by high KCl or exogenous glutamate treatment to enhance synaptic activities. However, the pretreatment of MK801 to block synaptic NMDA receptors abolished the glutamate-induced reduction of the $I_A$ peak, indicating the necessity of synaptic activation for the reduction of somatic $I_A$. This was again confirmed by glycine treatment, showing a significant reduction of the somatic $I_A$ peak. Additionally, the gating property of $I_A$ channels was also sensitive to the activation of synaptic NMDA receptors, showing the hyperpolarizing shift in inactivation kinetics. These results suggest that synaptic LTP possibly potentiates somatic excitability via downregulating $I_A$ channels in expression and gating kinetics. The consequential changes of somatic excitability following the activity-dependent modulation of synaptic responses may be a series of processings for neuronal functions to determine outputs in memory mechanisms or pathogenic conditions.

An Analysis of the Definition and the Meaning Used for the Terms of Heat and Thermal Energy in the Science Textbooks (과학과 교과서에 나타난 열과 열에너지 용어의 정의 및 사용 의미 분석)

  • Kim, Serim;Park, Jong-Yoon
    • Journal of the Korean Chemical Society
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    • v.62 no.3
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    • pp.214-225
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    • 2018
  • In this study, we tried to find out how heat and thermal energy terms are defined and used in Korean science textbooks, and to see if there are any differences in the meaning of these terms used in different areas of science. For this purpose, the contents of 52 science textbooks of elementary, middle and high school published by the 2009 revised curriculum were analyzed. The definition of the term heat is given in the middle school Science(1) and the high school Physics I and II textbooks. Most textbooks define heat as "energy transferred due to a temperature difference (Type I)". Only one textbook of Physics I defines heat as "transfer of energy due to a temperature difference (Type II)". The definition of thermal energy is mostly presented in the middle school Science (2) and the high school Physics I textbooks. Physics I textbooks define the thermal energy as "molecular kinetic energy (Type III)", while Science(2) textbooks define it as Type I or "energy causes temperature change or phase transition of matter (Type IV)". In the texts of textbooks, heat is mainly used as the meaning of Type I or Type III. Thermal energy is mainly used as Type III, but it is also used as Type I in the high school Physics and Chemistry textbooks. The meanings of heat and thermal energy terms used are differed by the area of science. They are mainly used as type I or type III in Physics and Chemistry textbooks, and used as type III in Life Science and Earth Science textbooks.

SOME ESTIMATES FOR GENERALIZED COMMUTATORS OF MULTILINEAR CALDERÓN-ZYGMUND OPERATORS

  • Honghai Liu;Zengyan Si;Ling Wang
    • Bulletin of the Korean Mathematical Society
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    • v.60 no.2
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    • pp.541-560
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    • 2023
  • Let T be an m-linear Calderón-Zygmund operator. $T_{{\vec{b}S}}$ is the generalized commutator of T with a class of measurable functions {bi}i=1. In this paper, we will give some new estimates for $T_{{\vec{b}S}}$ when {bi}i=1 belongs to Orlicz-type space and Lipschitz space, respectively.

Toll-like Receptor3-mediated Induction of Chemokines in Salivary Epithelial Cells

  • Li, Jingchao;Jeong, Mi-Young;Bae, Ji-Hyun;Shin, Yong-Hwan;Jin, Meihong;Hang, Sung-Min;Lee, Jeong-Chai;Lee, Sung-Joong;Park, Kyung-Pyo
    • The Korean Journal of Physiology and Pharmacology
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    • v.14 no.4
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    • pp.235-240
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    • 2010
  • Toll-like receptors (TLRs) functionally expressed in salivary epithelial cells, but their roles remain elusive. Among TLRs family, TLR3 is activated by dsRNA, a byproduct of viral infection. The aim of this study was to investigate the role of TLR3 in the inflammatory immune responses using HSG cells. Reverse transcriptase-polymerase chain reaction (RT-PCR), real-time PCR and ELISA were performed to identify expression of TLRs and TLR3-mediated chemokine inductions. The chemotaxis assay of activated T lymphocytes was also performed. Treatment of HSG cells with polyinosinic: polycytidylic acid (poly(I:C)) significantly increased interferon-$\gamma$-inducible protein 10 (IP-10), interferoninducible T-cell $\alpha$ chemoattractant (I-TAC), and regulated on activation, normal T-cells expressed and secreted (RANTES) gene expressions in a concentration-dependent manner. Anti-TLR3 antibody blocked the increases of IP-10 and I-TAC genes. Poly(I:C)-induced increases of IP-10 and I-TAC were also confirmed at protein levels from cell lysates, but their release into extracellular medium was detected only in IP-10. We found that the culture media from HSG cells stimulated with poly(I:C) significantly increases T lymphocyte migration. Our results suggest that TLR3 plays an important role in chemokine induction, particularly IP-10, in salivary epithelial cells.