• Title/Summary/Keyword: differential mechanism

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Analysis of the Correlation between Expressions of HSP90α, HSP90β, and GRP94, and the Clinicopathologic Characteristics in Tissues of Non-Small Cell Lung Cancer Patients (비소세포 폐암 환자 조직에서 Hsp90α, Hsp90β, GRP94의 발현과 임상병리학적 특성과의 상관관계 분석)

  • Kim, Mi Kyeong
    • Korean Journal of Clinical Laboratory Science
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    • v.49 no.4
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    • pp.460-469
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    • 2017
  • Heat shock proteins (HSPs) are induced as a self-defense mechanism of cells when exposed to various external stresses, such as high fever, infection, free radicals, and heavy metals. They affect the prognosis in the process of tumor formation. HSP is classified into four families: HSP27, HSP60, HSP90, and HSP100, depending on molecular weight. Heat shock protein 90 (HSP90), a molecular chaperone, plays an important role in the cellular protection against various stressful stimuli and in the regulation of cell cycle progression and apoptosis. In the present study, we assessed the differential expression of HSP90 family proteins in non-small cell lung cancer (NSCLC), and the correlation of their expression levels with clinicopathologic factors and patient survival rates. The result of this study can be summarized as follows; $HSP90{\alpha}$ showed higher expression in patients with no lymphovascular invasion (p=0.014). $HSP90{\beta}$ showed a higher expression of squamous cell carcinoma (p=0.003), and an over expression of glucose-related protein (GRP94) was significantly associated with poor differentiation (p=0.048). However, none of the HSP90 proteins showed a significant association with the survival status in patients with NSCLC. This study also indicates that $HSP90{\alpha}$ might contribute more to the carcinogenesis of NSCLC than $HSP90{\beta}$, and GRP94 and isoform selectivity should be considered when HSP90 inhibitors are studied or utilized in the treatment of NSCLC.

The effect of antipsychotics and antidepressants on the TREK2 channel (TREK2 채널에 대한 항정신성약물 및 항우울제의 효과)

  • Kwak, Ji-Yeon;Kim, Yang-Mi
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.13 no.5
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    • pp.2125-2132
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    • 2012
  • Fluoxetine and tianeptine are commonly used as antidepressants (AD), and haloperidol and risperidone are widely used as antipsychotic drugs (APD), and it modulates various ion channels. TREK2 channel subfamily is very similar to physiological properties of TREK1 channel which can play important roles in the pathophysiology of mental disorders such as depression and schizophrenia, therefore, the pharmacological effect of psychiatric and depression drug on TREK2 channel may be similar to those of TREK1. Using the excised inside-out patch-clamp technique, we have examined the effects of APD and AD on cloned TREK2 channel expressed CHO cells. Fluoxetine (selective serotonin release inhibitor, SSRI) inhibited the TREK2 channel in a concentration-dependent manner ($IC_{50}$ $13{\mu}M$), whereas selective serotonin reuptake enhancer (SSRE) tianeptine increased without reducing the TREK2 channel activity. Haloperidol also inhibited the TREK2 channel in a concentration-dependent manner ($IC_{50}$ $44{\mu}M$), whereas even higher concentration ($100{\mu}M$) of risperidone did not completely inhibit on the activity. This study showed that TREK2 channel was preferentially blocked by fluoxetine rather than tianeptine, and inhibited by haloperidol rather than risperidone, suggesting differential effect of TREK2 channels by APD and AD may contribute to some mechanism of adverse side effects.

Effects of Exogenous Insulin-like Growth Factor 2 on Neural Differentiation of Parthenogenetic Murine Embryonic Stem Cells

  • Choi, Young-Ju;Park, Sang-Kyu;Kang, Ho-In;Roh, Sang-Ho
    • Reproductive and Developmental Biology
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    • v.36 no.1
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    • pp.33-37
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    • 2012
  • Differential capacity of the parthenogenetic embryonic stem cells (PESCs) is still under controversy and the mechanisms of its neural induction are yet poorly understood. Here we demonstrated neural lineage induction of PESCs by addition of insulin-like growth factor-2 (Igf2), which is an important factor for embryo organ development and a paternally expressed imprinting gene. Murine PESCs were aggregated to embryoid bodies (EBs) by suspension culture under the leukemia inhibitory factor-free condition for 4 days. To test the effect of exogenous Igf2, 30 ng/ml of Igf2 was supplemented to EBs induction medium. Then neural induction was carried out with serum-free medium containing insulin, transferrin, selenium, and fibronectin complex (ITSFn) for 12 days. Normal murine embryonic stem cells derived from fertilized embryos (ESCs) were used as the control group. Neural potential of differentiated PESCs and ESCs were analyzed by immunofluorescent labeling and real-time PCR assay (Nestin, neural progenitor marker; Tuj1, neuronal cell marker; GFAP, glial cell marker). The differentiated cells from both ESC and PESC showed heterogeneous population of Nestin, Tuj1, and GFAP positive cells. In terms of the level of gene expression, PESC showed 4 times higher level of GFAP expression than ESCs. After exposure to Igf2, the expression level of GFAP decreased both in derivatives of PESCs and ESCs. Interestingly, the expression level of $Tuj1$ increased only in ESCs, not in PESCs. The results show that IGF2 is a positive effector for suppressing over-expressed glial differentiation during neural induction of PESCs and for promoting neuronal differentiation of ESCs, while exogenous Igf2 could not accelerate the neuronal differentiation of PESCs. Although exogenous Igf2 promotes neuronal differentiation of normal ESCs, expression of endogenous $Igf2$ may be critical for initiating neuronal differentiation of pluripotent stem cells. The findings may contribute to understanding of the relationship between imprinting mechanism and neural differentiation and its application to neural tissue repair in the future.

Stem Cells and Cell-Cell Communication in the Understanding of the Role of Diet and Nutrients in Human Diseases

  • Trosko James E.
    • Journal of Food Hygiene and Safety
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    • v.22 no.1
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    • pp.1-14
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    • 2007
  • The term, "food safety", has traditionally been viewed as a practical science aimed at assuring the prevention acute illnesses caused by biological microorganisms, and only to a minor extent, chronic diseases cause by chronic low level exposures to natural and synthetic chemicals or pollutants. "food safety" meant to prevent microbiological agents/toxins in/on foods, due to contamination any where from "farm to Fork", from causing acute health effects, especially to the young, immune-compromised, genetically-predisposed and elderly. However, today a broader view must also include the fact that diet, perse (nutrients, vitamins/minerals, calories), as well as low level toxins and pollutant or supplemented synthetic chemicals, can alter gene expressions of stem/progenitor/terminally-differentiated cells, leading to chronic inflammation and other mal-functions that could lead to diseases such as cancer, diabetes, atherogenesis and possibly reproductive and neurological disorders. Understanding of the mechanisms by which natural or synthetic chemical toxins/toxicants, in/on food, interact with the pathogenesis of acute and chronic diseases, should lead to a "systems" approach to "food safety". Clearly, the interactions of diet/food with the genetic background, gender, and developmental state of the individual, together with (a) interactions of other endogenous/exogenous chemicals/drugs; (b) the specific biology of the cells being affected; (c) the mechanisms by which the presence or absence of toxins/toxicants and nutrients work to cause toxicities; and (d) how those mechanisms affect the pathogenesis of acute and/or chronic diseases, must be integrated into a "system" approach. Mechanisms of how toxins/toxicants cause cellular toxicities, such as mutagenesis; cytotoxicity and altered gene expression, must take into account (a) irreversible or reversal changes caused by these toxins or toxicants; (b)concepts of thresholds or no-thresholds of action; and (c) concepts of differential effects on stem cells, progenitor cells and terminally differentiated cells in different organs. This brief Commentary tries to illustrate this complex interaction between what is on/in foods with one disease, namely cancer. Since the understanding of cancer, while still incomplete, can shed light on the multiple ways that toxins/toxicants, as well as dietary modulation of nutrients/vitamins/metals/ calories, can either enhance or reduce the risk to cancer. In particular, diets that alter the embryo-fetal micro-environment might dramatically alter disease formation later in life. In effect "food safety" can not be assessed without understanding how food could be 'toxic', or how that mechanism of toxicity interacts with the pathogenesis of any disease.

Current Status of the KMTNet Active Nuclei Variability Survey (KANVaS)

  • Kim, Joonho;Karouzos, Marios;Im, Myungshin
    • The Bulletin of The Korean Astronomical Society
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    • v.41 no.1
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    • pp.54.1-54.1
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    • 2016
  • Multi-wavelength variability is a staple of active galactic nuclei (AGN). Optical variability probes the nature of the central engine of AGN at smaller linear scales than conventional imaging and spectroscopic techniques. Previous studies have shown that optical variability is more prevalent at longer timescales and at shorter wavelengths. Intra-night variability can be explained through the damped random walk model but small samples and inhomogeneous data have made constraining this model hard. To understand the properties and physical mechanism of intra-night optical variability, we are performing the KMTNet Active Nuclei Variability Survey (KANVaS). Using KMTNet, we aim to study the intra-night variability of ~1000 AGN at a magnitude depth of ~19mag in R band over a total area of ${\sim}24deg^2$ on the sky. Test data in the COSMOS, XMM-LSS, and S82-2 fields was obtained over 4, 6, and 8 nights respectively during 2015, in B, V, R, and I bands. Each night was composed of 5-13 epoch with ~30 min cadence and 80-120 sec exposure times. As a pilot study, we analyzed data in the COSMOS field where we reach a magnitude depth of ~19.5 in R band (at S/N~100) with seeing varying between 1.5-2.0 arcsec. We used the Chandra-COSMOS catalog to identify 166 AGNs among 549 AGNs at B<23. We performed differential photometry between the selected AGN and nearby stars, achieving photometric uncertainty ~0.01mag. We employ various standard time-series analysis tools to identify variable AGN, including the chi-square test. Preliminarily results indicate that intra-night variability is found for ~17%, 17%, 8% and 7% of all X-ray selected AGN in the B, V, R, and I band, respectively. The majority of the identified variable AGN are classified as Type 1 AGN, with only a handful of Type 2 AGN showing evidence for variability. The work done so far confirms there are more variable AGN at shorter wavelengths and that intra-night variability most likely originates in the accretion disk of these objects. We will briefly discuss the quality of the data, challenges we encountered, solutions we employed for this work, and our updated future plans.

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Classification of a Volumetric MRI Using Gibbs Distributions and a Line Model (깁스분포와 라인모델을 이용한 3차원 자기공명영상의 분류)

  • Junchul Chun
    • Investigative Magnetic Resonance Imaging
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    • v.2 no.1
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    • pp.58-66
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    • 1998
  • Purpose : This paper introduces a new three dimensional magnetic Resonance Image classification which is based on Mar kov Random Field-Gibbs Random Field with a line model. Material and Methods : The performance of the Gibbs Classifier over a statistically heterogeneous image can be improved if the local stationary regions in the image are disassociated from each other through the mechanism of the interaction parameters defined at the local neighborhood level. This usually involves the construction of a line model for the image. In this paper we construct a line model for multisignature images based on the differential of the image which can provide an a priori estimate of the unobservable line field, which may lie in regions with significantly different statistics. the line model estimated from the original image data can in turn be used to alter the values of the interaction parameters of the Gibbs Classifier. Results : MRF-Gibbs classifier for volumetric MR images is developed under the condition that the domain of the image classification is $E^{3}$ space rather thatn the conventional $E^{2}$ space. Compared to context free classification, MRF-Gibbs classifier performed better in homogeneous and along boundaries since contextual information is used during the classification. Conclusion : We construct a line model for multisignature, multidimensional image and derive the interaction parameter for determining the energy function of MRF-Gibbs classifier.

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A Study on the Analysis of Energy Voucher Effects Using Micro-household Data (가구부문 미시자료를 활용한 에너지바우처 효과 추정에 관한 연구)

  • Lee, Eun Sol;Park, Kwang Soo;Lee, Yoon;Yoon, Tae Yeon
    • Environmental and Resource Economics Review
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    • v.28 no.4
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    • pp.527-556
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    • 2019
  • In Korea, nearly 100 billion won is spent annually under the name of energy voucher on 600,000 households for the last five years, and this is a unique case and hard to monitor worldwide. Therefore, no studies have been conducted to assess impacts of the energy voucher on energy consumption and cost burden alleviation for beneficiaries. This paper aims to demonstrate the effectiveness of energy vouchers in terms of energy expense. The propensity score matching was conducted on samples of low-income households based on the Korea Welfare Panel. Then, simple Difference-In-Differences and Fixed-Effect Difference-In-Differences models were applied to estimate the effect of energy vouchers. In results, the beneficiaries of energy vouchers would spend an additional 4,371~4,870 won per month on energy consumption. The ratio is equivalent to 51.9~57.7 percent of the aid, which is also the highest when compared with 23~56 percent of U.S. Food Stamp. In terms of energy welfare, voucher payment could become one of the best management practices. However, identifying the blind spots as non-reciprocal households and expanding the differential support mechanism that reflects the energy consumption environment should be solved in the future.

Genome-wide identification and analysis of long noncoding RNAs in longissimus muscle tissue from Kazakh cattle and Xinjiang brown cattle

  • Yan, Xiang-Min;Zhang, Zhe;Liu, Jian-Bo;Li, Na;Yang, Guang-Wei;Luo, Dan;Zhang, Yang;Yuan, Bao;Jiang, Hao;Zhang, Jia-Bao
    • Animal Bioscience
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    • v.34 no.11
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    • pp.1739-1748
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    • 2021
  • Objective: In recent years, long noncoding RNAs (lncRNAs) have been identified in many species, and some of them have been shown to play important roles in muscle development and myogenesis. However, the differences in lncRNAs between Kazakh cattle and Xinjiang brown cattle remain undefined; therefore, we aimed to confirm whether lncRNAs are differentially expressed in the longissimus dorsi between these two types of cattle and whether differentially expressed lncRNAs regulate muscle differentiation. Methods: We used RNA-seq technology to identify lncRNAs in longissimus muscles from these cattle. The expression of lncRNAs were analyzed using StringTie (1.3.1) in terms of the fragments per kilobase of transcript per million mapped reads values of the encoding genes. The differential expression of the transcripts in the two samples were analyzed using the DESeq R software package. The resulting false discovery rate was controlled by the Benjamini and Hochberg's approach. KOBAS software was utilized to measure the expression of different genes in Kyoto encyclopedia of genes and genomes pathways. We randomly selected eight lncRNA genes and validated them by quantitative reverse transcription polymerase chain reaction (RT-qPCR). Results: We found that 182 lncRNA transcripts, including 102 upregulated and 80 downregulated transcripts, were differentially expressed between Kazakh cattle and Xinjiang brown cattle. The results of RT-qPCR were consistent with the sequencing results. Enrichment analysis and functional annotation of the target genes revealed that the differentially expressed lncRNAs were associated with the mitogen-activated protein kinase, Ras, and phosphatidylinositol 3-kinase (PI3k)/Akt signaling pathways. We also constructed a lncRNA/mRNA coexpression network for the PI3k/Akt signaling pathway. Conclusion: Our study provides insights into cattle muscle-associated lncRNAs and will contribute to a more thorough understanding of the molecular mechanism underlying muscle growth and development in cattle.

Perioperative stress prolong post-surgical pain via miR-339-5p targeting oprm1 in the amygdala

  • Zhu, Yi;Sun, Mei;Liu, Peng;Shao, Weidong;Xiong, Ming;Xu, Bo
    • The Korean Journal of Pain
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    • v.35 no.4
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    • pp.423-432
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    • 2022
  • Background: The decreased expression of mu-opioid receptors (MOR) in the amygdala may be a key molecular in chronic post-surgical pain (CPSP). It is known that miR-339-5p expression in the amygdala of a stressed rat model was increased. Analyzed by RNAhybrid, miR-339-5p could target opioid receptor mu 1 (oprm1) which codes MOR directly. So, the authors hypothesized that miR-339-5p could regulate the expression of MOR via targeting oprm1 and cause the effects to CPSP. Methods: To simulate perioperative short-term stress, a perioperative stress prolongs incision-induced pain hypersensitivity without changing basal pain perception rat model was built. A pmiR-RB-REPORTTM dual luciferase assay was taken to verify whether miR-339-5p could act on oprm1 as a target. The serum glucocorticoid level of rats was test. Differential expressions of MOR, GFAP, and pERK1/2 in each group of the rats' amygdala were tested, and the expressions of miR-339-5p in each group of rats' amygdalas were also measured. Results: Perioperative stress prolonged the recovery time of incision pain. The expression of MOR was down-regulated in the amygdala of rats in stress + incision (S + IN) group significantly compared with other groups (P < 0.050). miR-339-5p was up-regulated in the amygdala of rats in group S + IN significantly compared with other groups (P < 0.050). miR-339-5p acts on oprm1 3'UTR and take MOR mRNA as a target. Conclusions: Perioperative stress could increase the expression of miR-339-5p, and miR-339-5p could cause the expression of MOR to decrease via targeting oprm1. This regulatory pathway maybe an important molecular mechanism of CPSP.

Up-regulation of an ERP component toward racial-outgroup faces in Koreans but not in non-Korean visitors (한국인과 한국에 거주하는 외국인간의 타인종 얼굴에 대한 ERP 요소의 흥분성 조절 비교)

  • Kim, Hyuk;Lee, Kang-hee;Kim, Hyun-Taek;Choi, June-Seek
    • Korean Journal of Cognitive Science
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    • v.33 no.2
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    • pp.95-107
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    • 2022
  • Facial processing of different racial origin has been investigated at various levels including perceptual, emotional, and socio-cultural processing. Particularly, a good deal of studies have been conducted to show "other race effect (ORE)" to indicate that subtle facial information such as identity or emotional expressions are often under-processed in racial out-group members. However, few studies have investigated whether attentional modulation toward racial out-group faces could explain ORE. We investigated whether novelty-driven attentional mechanism is involved in face perception using event-related potential (ERP). Twenty-two Korean (KR) and nine Caucasian-American (AM) participants were presented with emotional faces from the two racial origins while they performed a gender categorization task. KRs showed significantly greater P3 amplitudes to AM than to KR faces indicating that the early attentional processing underlies differential perception of racial out-group faces. Interestingly, P3 was not up-regulated in the AM subjects when they were presented with KR faces, perhaps due to massive habituation to KR faces during everyday social interaction. These results indicate that racial out-group faces are highly salient stimuli which automatically occupy attentional resources, but easily habituated with repeated exposure to the racial-out group.