• Title/Summary/Keyword: Molecular signature

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DNA칩을 이용한 위암의 진단 및 예후 측정

  • Eom Won-Seok
    • Proceedings of the Korean Society for Bioinformatics Conference
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    • 2006.02a
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    • pp.11-18
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    • 2006
  • 바이오칩의 대표 주자인 DNA 칩은 점차 분자생물학의 주요 도구로 인식되고 있다. 쓰임새 또한 다양해져 기초 생물학, 기능 유전체학 연구뿐만 아니라 임상 현장에서의 적용을 위한 연구가 활발히 진행되고 있다. 임상분야에서 최근 주목 받고 있는 분야가 DNA 칩을. 이용한 질병진단 및 예후 측정이다. 개별 환자 세포의 분자유전학적 상태는 DNA 칩의 유전체 프로파일링(genome-wide profiling)으로 상세히 파악될 수 있으므로, DNA 칩은 질병의 세부아형 진단, 약물에 대한 개인 민감도 측정, 정확한 예후 측정을 통한 환자의 세심한 관리 등 미래 의료의 핵심이라 할 수 있는 개인별 맞춤 치료(personalized medicare)를 가능하게 하는데 지대한 역할을 할 것으로 기대되고 있다. 특히 수많은 질병 중에서 현대인의 난치병으로 손꼽히는 암은 DNA 칩 분석의 주요 적용 대상이다. 암에 연관된 복잡한 메커니즘을 기존의 단일 표지자로 진단하는 데는 한계가 있기 때문에, DNA 칩을 이용해 질병의 특정 phenotype과 관련 있는 암의 특이 패턴을 전사체 수준에서 분석하여 새로운 형태의 분자유전학적 표지자(transcriptional molecular signature)를 발굴하는 것이다 본 발표에서는 이러한 연구에 쓰이는 DNA 칩 분석 방법들과 실제 위암 데이터에 적용한 사례에 대해 논의하고자 한다. 연세의대 암전이 연구센터의 17K cDNA 칩을 이용하였으며, 진단 및 예후 측정을 위한 여러 분석 방법을 수행하였다.

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CD133 Regulates IL-1β Signaling and Neutrophil Recruitment in Glioblastoma

  • Lee, Seon Yong;Kim, Jun-Kyum;Jeon, Hee-Young;Ham, Seok Won;Kim, Hyunggee
    • Molecules and Cells
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    • v.40 no.7
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    • pp.515-522
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    • 2017
  • CD133, a pentaspan transmembrane glycoprotein, is generally used as a cancer stem cell marker in various human malignancies, but its biological function in cancer cells, especially in glioma cells, is largely unknown. Here, we demonstrated that forced expression of CD133 increases the expression of IL-$1{\beta}$ and its downstream chemokines, namely, CCL3, CXCL3 and CXCL5, in U87MG glioma cells. Although there were no apparent changes in cell growth and sphere formation in vitro and tumor growth in vivo, in vitro trans-well studies and in vivo tumor xenograft assays showed that neutrophil recruitment was markedly increased by the ectopic expression of CD133. In addition, the clinical relevance between CD133 expression and IL-$1{\beta}$ gene signature was established in patients with malignant gliomas. Thus, these results imply that glioma cells expressing CD133 are capable of modulating tumor microenvironment through the IL-$1{\beta}$ signaling pathway.

Use of DNA-Specific Anthraquinone Dyes to Directly Reveal Cytoplasmic and Nuclear Boundaries in Live and Fixed Cells

  • Edward, Roy
    • Molecules and Cells
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    • v.27 no.4
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    • pp.391-396
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    • 2009
  • Image-based, high-content screening assays demand solutions for image segmentation and cellular compartment encoding to track critical events - for example those reported by GFP fusions within mitosis, signalling pathways and protein translocations. To meet this need, a series of nuclear/cytoplasmic discriminating probes have been developed: DRAQ5$^{TM}$ and CyTRAK Orange$^{TM}$. These are spectrally compatible with GFP reporters offering new solutions in imaging and cytometry. At their most fundamental they provide a convenient fluorescent emission signature which is spectrally separated from the commonly used reporter proteins (e.g. eGFP, YFP, mRFP) and fluorescent tags such as Alexafluor 488, fluorescein and Cy2. Additionally, they do not excite in the UV and thus avoid the complications of compound UV-autofluorescence in drug discovery whilst limiting the impact of background sample autofluorescence. They provide a convenient means of stoichiometrically labelling cell nuclei in live cells without the aid of DMSO and can equally be used for fixed cells. Further developments have permitted the simultaneous and differential labelling of both nuclear and cytoplasmic compartments in live and fixed cells to clearly render the precise location of cell boundaries which may be beneficial for quantitative expression measurements, cell-cell interactions and most recently compound in vitro toxicology testing.

A Study on the Impact Behavior of Bulletproof Materials According to the Combining Method

  • Jihyun Kwon;Euisang Yoo
    • Elastomers and Composites
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    • v.57 no.4
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    • pp.157-164
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    • 2022
  • Representative bulletproof materials, such as aramid or ultra-high molecular weight polyethylene(UHMWPE), have excellent strength and modulus in the plane direction but are very vulnerable to forces applied in the thickness direction. This paper reports a study on the effects of reinforcement in the thickness direction when bulletproof composite fabrics are prepared to improve their performance. Aramid and UHMWPE fabrics were combined using the film-bonding, needle-punching, or stitching methods and then subjected to low-velocity projectile and ball-drop impact tests. The results of the low-velocity projectile test indicated that the backface signature(BFS) decreased by up to 29.2% in fabrics obtained via the film-bonding method. However, the weight of the film-bonded fabric increased by approximately 23% compared with that obtained by simple lamination, and the fabric stiffened on account of the binder. Flexibility, light weight for wearability, and excellent bulletproof performance are very important factors in the development of bulletproof materials. When the needle-punching method was used, the BFS increased as the fibers sustained damage by the needle. When the composite fabrics were combined by stitching, no significant difference in weight and thickness was observed, and the BFS showed similar results. When a diagonal stitching pattern was employed, the BFS decreased as the stitching density increased. By contrast, when a diamond stitching pattern was used, the fabric fibers were damaged and the BFS increased as the stitching density increased.

Ginsenoside Rg4 Enhances the Inductive Effects of Human Dermal Papilla Spheres on Hair Growth Via the AKT/GSK-3β/β-Catenin Signaling Pathway

  • Lee, Yun Hee;Choi, Hui-Ji;Kim, Ji Yea;Kim, Ji-Eun;Lee, Jee-Hyun;Cho, So-Hyun;Yun, Mi-Young;An, Sungkwan;Song, Gyu Yong;Bae, Seunghee
    • Journal of Microbiology and Biotechnology
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    • v.31 no.7
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    • pp.933-941
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    • 2021
  • Ginsenoside Rg4 is a rare ginsenoside that is naturally found in ginseng, and exhibits a wide range of biological activities including antioxidant and anti-inflammatory properties in several cell types. The purpose of this study was to use an in vivo model of hair follicle (HF)-mimic based on a human dermal papilla (DP) spheroid system prepared by three-dimensional (3D) culture and to investigate the effect of Rg4 on the hair-inductive properties of DP cells. Treatment of the DP spheroids with Rg4 (20 to 50 ㎍/ml) significantly increased the viability and size of the DP spheres in a dose-dependent manner. Rg4 also increased the mRNA and protein expression of DP signature genes that are related to hair growth including ALP, BMP2, and VCAN in the DP spheres. Analysis of the signaling molecules and luciferase reporter assays further revealed that Rg4 induces the activation of phosphoinositide 3-kinase (PI3K)/AKT and the inhibitory phosphorylation of GSK3β, which activates the WNT/β-catenin signaling pathway. These results correlated with not only the increased nuclear translocation of β-catenin following the treatment of the DP spheres with Rg4 but also the significant elevation of mRNA expression of the downstream target genes of the WNT/β-catenin pathway including WNT5A, β-catenin, and LEF1. In conclusion, these results demonstrated that ginsenoside Rg4 promotes the hair-inductive properties of DP cells by activating the AKT/GSK3β/β-catenin signaling pathway in DP spheres, suggesting that Rg4 could be a potential natural therapy for hair growth.

Molecular Cloning and Expression Analysis of Red-spotted Grouper, Epinephelus akaara Hsp70 (수온변화에 따른 붉바리(Epinephelus akaara)의 heat shock protein (Hsp) 70 mRNA 발현)

  • Min, Byung Hwa;Hur, Jun Wook;Park, Hyung Jun
    • Journal of Life Science
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    • v.28 no.6
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    • pp.639-647
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    • 2018
  • A new heat shock protein 70 was identified in red-spotted grouper (Epinephelus akaara) based on an expression analysis. The cDNA of red-spotted grouper Hsp70 (designated RgHsp70) was cloned by the rapid amplification of cDNA ends (RACE) techniques. The full-length of RgHsp70 cDNA was 2,152 bp, consisting of a 5'-terminal untranslated region (UTR) of 105 bp, a 3'-terminal UTR of 274 bp, and an open reading frame (ORF) of 1,773 bp that encode a polypeptide of 590 amino acids with a theoretical molecular weight of 64.9 kDa and an estimated isoelectric point of 5.2. Multiple alignment and phylogenetic analyses revealed that the RgHsp70 gene shares a high similarity with other Hsp70 fish genes. RgHsp70 contained all three classical Hsp70 family signatures. The results indicated the RgHsp70 is a member of the heat shock protein 70 family. RgHsp70 mRNA was predominately expressed in the liver, with reduced expression noted in the head-kidney tissues. The expression analysis of different water temperatures (21, 18, 15 and $12^{\circ}C$) for sampled livers revealed that expression gradually increased at $12^{\circ}C$ compared to $21^{\circ}C$. In this study, the effects of water temperature lowering on the physiological conditions were investigated, and the results revealed that novel RgHsp70 may be an important molecule involved in stress responses.

CHEMICAL PROPERTIES OF CORES IN DIFFERENT ENVIRONMENTS; THE ORION A, B AND λ ORIONIS CLOUDS

  • Yi, Hee-Weon;Lee, Jeong-Eun;Liu, Tie;Kim, Kee-Tae
    • The Bulletin of The Korean Astronomical Society
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    • v.44 no.1
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    • pp.42.1-42.1
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    • 2019
  • We observed 80 dense cores ($N(H_2)$ > $10^{22}cm^{-2}$) in the Orion molecular cloud complex which contains the Orion A (39 cores), B (26 cores), and ${\lambda}$ Orionis (15 cores) clouds. We investigate the behavior of the different molecular tracers and look for chemical variations of cores in the three clouds in order to systematically investigate the effects of stellar feedback. The most commonly detected molecular lines (with the detection rates higher than 50%) are $N_2H^+$, $HCO^+$, $H^{13}CO^+$, $C_2H$, HCN, and $H_2CO$. The detection rates of dense gas tracers, $N_2H^+$, $HCO^+$, $H^{13}CO^+$, and $C_2H$ show the lowest values in the ${\lambda}$ Orionis cloud. We find differences in the D/H ratio of $H_2CO$ and the $N_2H^+/HCO^+$ abundance ratios among the three clouds. Eight starless cores in the Orion A and B clouds exhibit high deuterium fractionations, larger than 0.10, while in the ${\lambda}$ Orionis cloud, no cores reveal the high ratio. These chemical properties could support that cores in the ${\lambda}$ Orionis cloud are affected by the photo-dissociation and external heating from the nearby H II region. An unexpected trend was found in the $[N_2H^+]/[HCO^+]$ ratio with a higher median value in the ${\lambda}$ Orionis cloud than in the Orion A/B clouds than; typically, the $[N_2H^+]/[HCO^+]$ ratio is lower in higher temperatures and lower column densities. This could be explained by a longer timescale in the prestellar stage in the ${\lambda}$ Orionis cloud, resulting in more abundant nitrogen-bearing molecules. In addition to these chemical differences, the kinematical difference was also found among the three clouds; the blue excess, which is an infall signature found in optically thick line profiles, is 0 in the ${\lambda}$ Orionis cloud while it is 0.11 and 0.16 in the Orion A and B clouds, respectively. This result could be another evidence of the negative feedback of active current star formation to the next generation of star formation.

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Analysis of opposing histone modifications H3K4me3 and H3K27me3 reveals candidate diagnostic biomarkers for TNBC and gene set prediction combination

  • Park, Hyoung-Min;Kim, HuiSu;Lee, Kang-Hoon;Cho, Je-Yoel
    • BMB Reports
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    • v.53 no.5
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    • pp.266-271
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    • 2020
  • Breast cancer encompasses a major portion of human cancers and must be carefully monitored for appropriate diagnoses and treatments. Among the many types of breast cancers, triple negative breast cancer (TNBC) has the worst prognosis and the least cases reported. To gain a better understanding and a more decisive precursor for TNBC, two major histone modifications, an activating modification H3K4me3 and a repressive modification H3K27me3, were analyzed using data from normal breast cell lines against TNBC cell lines. The combination of these two histone markers on the gene promoter regions showed a great correlation with gene expression. A list of signature genes was defined as active (highly enriched H3K4me3), including NOVA1, NAT8L, and MMP16, and repressive genes (highly enriched H3K27me3), IRX2 and ADRB2, according to the distribution of these histone modifications on the promoter regions. To further enhance the investigation, potential candidates were also compared with other types of breast cancer to identify signs specific to TNBC. RNA-seq data was implemented to confirm and verify gene regulation governed by the histone modifications. Combinations of the biomarkers based on H3K4me3 and H3K27me3 showed the diagnostic value AUC 93.28% with P-value of 1.16e-226. The results of this study suggest that histone modification analysis of opposing histone modifications may be valuable toward developing biomarkers and targets for TNBC.

A SIGNATURE OF CHROMOSPHERIC ACTIVITY IN BROWN DWARFS: A RECENT RESULT FROM NIRLT MISSION PROGRAM

  • Sorahana, Satoko;Suzuki, Takeru K.;Yamamura, Issei
    • Publications of The Korean Astronomical Society
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    • v.32 no.1
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    • pp.131-133
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    • 2017
  • We present the latest results from the Mission Program NIRLT (PI: I.Yamamura), the near-infrared spectroscopy of brown dwarfs using the AKARI/IRC grism mode with the spectral resolution of ~ 120. The near-infrared spectra in the wavelength range between 2.5 and $5.0{\mu}m$ are especially important to study the brown dwarf atmospheres because of the presence of major molecular bands, including $CH_4$ at $3.3{\mu}m$, $CO_2$ at $4.2{\mu}m$, CO at $4.6{\mu}m$, and $H_2O$ around $2.7{\mu}m$. We observed 27 sources, and obtained 16 good spectra. Our model fitting reveals deviations between theoretical model and observed spectra in this wavelength range, which may be attributed to the physical condition of the upper atmosphere. The deviations indicate additional heating, which we hypothesize to be due to chromospheric activity. We test this effect by modifying the brown dwarf atmosphere model to artificially increase the temperature of the upper atmosphere, and compare the revised model with observed spectra of early- to mid-L type objects with $H{\alpha}$ emission. We find that the chemical structure of the atmosphere changes dramatically, and the heating model spectra of early-type brown dwarfs can be considerably improved to match the observed spectra. Our result suggests that chromospheric activity is essential to understand early-type brown dwarf atmospheres.

New surveillance concepts in food safety in meat producing animals: the advantage of high throughput 'omics' technologies - A review

  • Pfaffl, Michael W.;Riedmaier-Sprenzel, Irmgard
    • Asian-Australasian Journal of Animal Sciences
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    • v.31 no.7
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    • pp.1062-1071
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    • 2018
  • The misuse of anabolic hormones or illegal drugs is a ubiquitous problem in animal husbandry and in food safety. The ban on growth promotants in food producing animals in the European Union is well controlled. However, application regimens that are difficult to detect persist, including newly designed anabolic drugs and complex hormone cocktails. Therefore identification of molecular endogenous biomarkers which are based on the physiological response after the illicit treatment has become a focus of detection methods. The analysis of the 'transcriptome' has been shown to have promise to discover the misuse of anabolic drugs, by indirect detection of their pharmacological action in organs or selected tissues. Various studies have measured gene expression changes after illegal drug or hormone application. So-called transcriptomic biomarkers were quantified at the mRNA and/or microRNA level by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) technology or by more modern 'omics' and high throughput technologies including RNA-sequencing (RNA-Seq). With the addition of advanced bioinformatical approaches such as hierarchical clustering analysis or dynamic principal components analysis, a valid 'biomarker signature' can be established to discriminate between treated and untreated individuals. It has been shown in numerous animal and cell culture studies, that identification of treated animals is possible via our transcriptional biomarker approach. The high throughput sequencing approach is also capable of discovering new biomarker candidates and, in combination with quantitative RT-qPCR, validation and confirmation of biomarkers has been possible. These results from animal production and food safety studies demonstrate that analysis of the transcriptome has high potential as a new screening method using transcriptional 'biomarker signatures' based on the physiological response triggered by illegal substances.