• Title/Summary/Keyword: pathways

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Anti-inflammatory Effects of Phytochemicals Having Michael Addition Acceptors by the Modulation of Toll-like Receptor Signaling Pathways (Michael addition acceptor 그룹을 가지고 있는 phytochemicals의 toll-like receptor 신호전달체계 조절을 통한 항염증 효과)

  • Youn, Hyung-Sun
    • Korean Journal of Food Science and Technology
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    • v.41 no.5
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    • pp.477-482
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    • 2009
  • Toll-like receptors (TLRs) play a critical role in the induction of innate immune responses that are essential for host defense against invading microbial pathogens. In general, TLRs have two major downstream signaling pathways, namely MyD88- and TRIF-dependent pathways, leading to the activation of nuclear factor-${\kappa}B$ (NF-${\kappa}B$) and interferon regulatory factor 3 (IRF3) and the expression of inflammatory mediators. TLR4 dimerization is required for the activation of downstream signaling pathways and may be one of the first lines of regulation in activating TLR-mediated signaling pathways. In this paper, the molecular targets of curcumin, 6-shogaol, and cinnamaldehyde in TLR signaling pathways will be discussed. Curcumin, 6-shogaol, and cinnamaldehyde with ${\alpha},{\beta}$-unsaturated carbonyl groups inhibit the dimerization of TLR4 induced by lipopolysaccharide, resulting in the downregulation of NF-${\kappa}B$ and IRF3. These results suggest that phytochemicals with the structural motif conferring Michael addition inhibit TLR4 dimerization, suggesting a novel mechanism for the anti-inflammatory activity of phytochemicals.

Caenorhabditis elegans: A Model System for Anti-Cancer Drug Discovery and Therapeutic Target Identification

  • Kobet, Robert A.;Pan, Xiaoping;Zhang, Baohong;Pak, Stephen C.;Asch, Adam S.;Lee, Myon-Hee
    • Biomolecules & Therapeutics
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    • v.22 no.5
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    • pp.371-383
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    • 2014
  • The nematode Caenorhabditis elegans (C. elegans) offers a unique opportunity for biological and basic medical researches due to its genetic tractability and well-defined developmental lineage. It also provides an exceptional model for genetic, molecular, and cellular analysis of human disease-related genes. Recently, C. elegans has been used as an ideal model for the identification and functional analysis of drugs (or small-molecules) in vivo. In this review, we describe conserved oncogenic signaling pathways (Wnt, Notch, and Ras) and their potential roles in the development of cancer stem cells. During C. elegans germline development, these signaling pathways regulate multiple cellular processes such as germline stem cell niche specification, germline stem cell maintenance, and germ cell fate specification. Therefore, the aberrant regulations of these signaling pathways can cause either loss of germline stem cells or overproliferation of a specific cell type, resulting in sterility. This sterility phenotype allows us to identify drugs that can modulate the oncogenic signaling pathways directly or indirectly through a high-throughput screening. Current in vivo or in vitro screening methods are largely focused on the specific core signaling components. However, this phenotype-based screening will identify drugs that possibly target upstream or downstream of core signaling pathways as well as exclude toxic effects. Although phenotype-based drug screening is ideal, the identification of drug targets is a major challenge. We here introduce a new technique, called Drug Affinity Responsive Target Stability (DARTS). This innovative method is able to identify the target of the identified drug. Importantly, signaling pathways and their regulators in C. elegans are highly conserved in most vertebrates, including humans. Therefore, C. elegans will provide a great opportunity to identify therapeutic drugs and their targets, as well as to understand mechanisms underlying the formation of cancer.

Involvement of PI3K/AKT and MAPK Pathways for TNF-α Production in SiHa Cervical Mucosal Epithelial Cells Infected with Trichomonas vaginalis

  • Yang, Jung-Bo;Quan, Juan-Hua;Kim, Ye-Eun;Rhee, Yun-Ee;Kang, Byung-Hyun;Choi, In-Wook;Cha, Guang-Ho;Yuk, Jae-Min;Lee, Young-Ha
    • Parasites, Hosts and Diseases
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    • v.53 no.4
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    • pp.371-377
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    • 2015
  • Trichomonas vaginalis induces proinflammation in cervicovaginal mucosal epithelium. To investigate the signaling pathways in $TNF-{\alpha}$ production in cervical mucosal epithelium after T. vaginalis infection, the phosphorylation of PI3K/AKT and MAPK pathways were evaluated in T. vaginalis-infected SiHa cells in the presence and absence of specific inhibitors. T. vaginalis increased $TNF-{\alpha}$ production in SiHa cells, in a parasite burden-dependent and incubation time-dependent manner. In T. vaginalis-infected SiHa cells, AKT, ERK1/2, p38 MAPK, and JNK were phosphorylated from 1 hr after infection; however, the phosphorylation patterns were different from each other. After pretreatment with inhibitors of the PI3K/AKT and MAPK pathways, $TNF-{\alpha}$ production was significantly decreased compared to the control; however, $TNF-{\alpha}$ reduction patterns were different depending on the type of PI3K/MAPK inhibitors. $TNF-{\alpha}$ production was reduced in a dose-dependent manner by treatment with wortmannin and PD98059, whereas it was increased by SP600125. These data suggested that PI3K/AKT and MAPK signaling pathways are important in regulation of $TNF-{\alpha}$ production in cervical mucosal epithelial SiHa cells. However, activation patterns of each pathway were different from the types of PI3K/MAPK pathways.

Role of MAPK Signaling Pathways in Regulating the Hydrophobin Cryparin in the Chestnut Blight Fungus Cryphonectria parasitica

  • So, Kum-Kang;Kim, Dae-Hyuk
    • Mycobiology
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    • v.45 no.4
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    • pp.362-369
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    • 2017
  • We assessed the regulation of cryparin, a class II hydrophobin, using three representative mitogen-activated protein kinase (MAPK) pathways in Cryphonectria parasitica. Mutation of the CpSlt2 gene, an ortholog of yeast SLT2 in the cell wall integrity (CWI) pathway, resulted in a dramatic decrease in cryparin production. Similarly, a mutant of the CpBck1 gene, a MAP kinase kinase kinase gene in the CWI pathway, showed decreased cryparin production. Additionally, mutation of the cpmk1 gene, an ortholog of yeast HOG1, showed decreased cryparin production. However, mutation of the cpmk2 gene, an ortholog of yeast Kss1/Fus3, showed increased cryparin production. The easy-wet phenotype and accumulation of the cryparin transcript in corresponding mutants were consistent with the cryparin production results. In silico analysis of the promoter region of the cryparin gene revealed the presence of binding motifs related to downstream transcription factors of CWI, HOG1, and pheromone responsive pathways including MADS-box- and Ste12-binding domains. Real-time reverse transcriptase PCR analyses indicated that both CpRlm1, an ortholog of yeast RLM1 in the CWI pathway, and cpst12, an ortholog of yeast STE12 in the mating pathway, showed significantly reduced transcription levels in the mutant strains showing lower cryparin production in C. prasitica. However, the transcription of CpMcm1, an ortholog of yeast MCM1, did not correlate with that of the mutant strains showing downregulation of cryparin. These results indicate that three representative MAPK pathways played a role in regulating cryparin production. However, regulation varied depending on the MAPK pathways: the CWI and HOG1 pathways were stimulatory, whereas the pheromone-responsive MAPK was repressive.

A comparison of five sets of overlapping and non-overlapping sliding windows for semen production traits in the Thai multibreed dairy population

  • Mattaneeya Sarakul;Mauricio A. Elzo;Skorn Koonawootrittriron;Thanathip Suwanasopee;Danai Jattawa;Thawee Laodim
    • Animal Bioscience
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    • v.37 no.3
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    • pp.428-436
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    • 2024
  • Objective: This study compared five distinct sets of biological pathways and associated genes related to semen volume (VOL), number of sperm (NS), and sperm motility (MOT) in the Thai multibreed dairy population. Methods: The phenotypic data included 13,533 VOL records, 12,773 NS records, and 12,660 MOT records from 131 bulls. The genotypic data consisted of 76,519 imputed and actual single nucleotide polymorphisms (SNPs) from 72 animals. The SNP additive genetic variances for VOL, NS, and MOT were estimated for SNP windows of one SNP (SW1), ten SNP (SW10), 30 SNP (SW30), 50 SNP (SW50), and 100 SNP (SW100) using a single-step genomic best linear unbiased prediction approach. The fixed effects in the model were contemporary group, ejaculate order, bull age, ambient temperature, and heterosis. The random effects accounted for animal additive genetic effects, permanent environment effects, and residual. The SNPs explaining at least 0.001% of the additive genetic variance in SW1, 0.01% in SW10, 0.03% in SW30, 0.05% in SW50, and 0.1% in SW100 were selected for gene identification through the NCBI database. The pathway analysis utilized genes associated with the identified SNP windows. Results: Comparison of overlapping and non-overlapping SNP windows revealed notable differences among the identified pathways and genes associated with the studied traits. Overlapping windows consistently yielded a larger number of shared biological pathways and genes than non-overlapping windows. In particular, overlapping SW30 and SW50 identified the largest number of shared pathways and genes in the Thai multibreed dairy population. Conclusion: This study yielded valuable insights into the genetic architecture of VOL, NS, and MOT. It also highlighted the importance of assessing overlapping and non-overlapping SNP windows of various sizes for their effectiveness to identify shared pathways and genes influencing multiple traits.

Inferring Pedestrian Level of Service for Pathways through Electrodermal Activity Monitoring

  • Lee, Heejung;Hwang, Sungjoo
    • International conference on construction engineering and project management
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    • 2022.06a
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    • pp.1247-1248
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    • 2022
  • Due to rapid urbanization and population growth, it has become crucial to analyze the various volumes and characteristics of pedestrian pathways to understand the capacity and level of service (LOS) for pathways to promote a better walking environment. Different indicators have been developed to measure pedestrian volume. The pedestrian level of service (PLOS), tailored to analyze pedestrian pathways based on the concept of the LOS in transportation in the Highway Capacity Manual, has been widely used. PLOS is a measurement concept used to assess the quality of pedestrian facilities, from grade A (best condition) to grade F (worst condition), based on the flow rate, average speed, occupied space, and other parameters. Since the original PLOS approach has been criticized for producing idealistic results, several modified versions of PLOS have also been developed. One of these modified versions is perceived PLOS, which measures the LOS for pathways by considering pedestrians' awareness levels. However, this method relies on survey-based measurements, making it difficult to continuously deploy the technique to all the pathways. To measure PLOS more quantitatively and continuously, researchers have adopted computer vision technologies to automatically assess pedestrian flows and PLOS from CCTV videos. However, there are drawbacks even with this method because CCTVs cannot be installed everywhere, e.g., in alleyways. Recently, a technique to monitor bio-signals, such as electrodermal activity (EDA), through wearable sensors that can measure physiological responses to external stimuli (e.g., when another pedestrian passes), has gained popularity. It has the potential to continuously measure perceived PLOS. In their previous experiment, the authors of this study found that there were many significant EDA responses in crowded places when other pedestrians acting as external stimuli passed by. Therefore, we hypothesized that the EDA responses would be significantly higher in places where relatively more dynamic objects pass, i.e., in crowded areas with low PLOS levels (e.g., level F). To this end, the authors conducted an experiment to confirm the validity of EDA in inferring the perceived PLOS. The EDA of the subjects was measured and analyzed while watching both the real-world and virtually created videos with different pedestrian volumes in a laboratory environment. The results showed the possibility of inferring the amount of pedestrian volume on the pathways by measuring the physiological reactions of pedestrians. Through further validation, the research outcome is expected to be used for EDA-based continuous measurement of perceived PLOS at the alley level, which will facilitate modifying the existing walking environments, e.g., constructing pathways with appropriate effective width based on pedestrian volume. Future research will examine the validity of the integrated use of EDA and acceleration signals to increase the accuracy of inferring the perceived PLOS by capturing both physiological and behavioral reactions when walking in a crowded area.

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Development of Multidimensional Analysis System for Bio-pathways (바이오 패스웨이 다차원 분석 시스템 개발)

  • Seo, Dongmin;Choi, Yunsoo;Jeon, Sun-Hee;Lee, Min-Ho
    • The Journal of the Korea Contents Association
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    • v.14 no.11
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    • pp.467-475
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    • 2014
  • With the development of genomics, wearable device and IT/NT, a vast amount of bio-medical data are generated recently. Also, healthcare industries based on big-data are booming and big-data technology based on bio-medical data is rising rapidly as a core technology for improving the national health and aged society. A pathway is the biological deep knowledge that represents the relations of dynamics and interaction among proteins, genes and cells by a network. A pathway is wildly being used as an important part of a bio-medical big-data analysis. However, a pathway analysis requires a lot of time and effort because a pathway is very diverse and high volume. Also, multidimensional analysis systems for various pathways are nonexistent even now. In this paper, we proposed a pathway analysis system that collects user interest pathways from KEGG pathway database that supports the most widely used pathways, constructs a network based on a hierarchy structure of pathways and analyzes the relations of dynamics and interaction among pathways by clustering and selecting core pathways from the network. Finally, to verify the superiority of our pathway analysis system, we evaluate the performance of our system in various experiments.

Conserved COG Pathways and Genes of 122 Species of Archaea (고세균 122종의 보존적 COG pathways와 유전자)

  • Dong-Geun Lee ;Sang-Hyeon Lee
    • Journal of Life Science
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    • v.33 no.11
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    • pp.944-949
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    • 2023
  • The purpose of this study was to identify conserved metabolic pathways and conserved genes in 122 archaeal species. Using the Clusters of Orthologous Groups of Proteins (COG) database of conserved genes, we analyzed whether 122 species had 63 COG metabolic pathways, the 822 COGs that compose them, and a total of 4,877 COGs. Archaeal ribosomal proteins were the most conserved in metabolic pathways. 46 COGs in seven COG pathways among 63 COG pathways and 20 COGs in others were conserved in 122 species. Some genes involved in cell wall and extracellular matrix synthesis, replication, transcription, translation, and protein metabolism were common to all 122 species. When the distance value of the phylogenetic tree was analyzed at the phylum level or class level, the average was the lowest at the class Halobacteria of the phylum Euryarchaeota. Standard deviation was high for the class Nitosospharia of the phylum Thaumarchaeota, the unclassified members of phylum Thaumarchaeota, the class Halobacteria of the phylum Euryarchaeota, the class Thermoprotei of the phylum Crenarchaeota, and other archaea. Furthermore, the phylogenetic tree analysis revealed six commonalities. The results of this study, along with data on conserved genes, could be used for drug development and gene selection for strain improvement.

Pathways Analysis of Gleditsia spina Extract on Changes of Gene Expression in Human Melanoma cells (조각자(皂角刺)가 악성흑색종 세포주에 미치는 영향)

  • Kim, Bu-Yeo;Lim, Se-Hyun;Lee, Byoung-Ho;Lim, Chi-Yeon;Kim, Yong-Seong;Cho, Su-In
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.22 no.3
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    • pp.47-62
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    • 2009
  • Glenditsia spina (GS) can resolve carbuncle, relive swelling, dispel wind and destroy parasites. For these reasons, GS has been widely used as dermatologic agent clinically. In this study, the specific pathways of anti-proliferative effect of GS on human derived melanoma cells were identified. The molecular profile was measured using microarray technique to identify up- or down-regulated genes in SK-MEL-2 cell line. Pathway analysis was done by listing percentage of pathway involvement, and the represented pathways were obtained from KEGG. The transcription factor binding sequences were obtained by Transfac database. By the promoter analysis, up-regulated genes by GS were mainly associated with MAPK, Regulation of actin cytoskeleton, Wnt, Focal adhesion and Long term potentiation pathway. Down-regulated genes by GS were mainly associated with MAPK and Antigen processing and presentation pathway. And some of the transcription factors like Sp1 and NF-Y in up-regulated genes and Oct-1 in down-regulated genes by GS also identified.

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Comparative Analysis of Scenarios for Reducing GHG Emissions in Korea by 2050 Using the Low Carbon Path Calculator (저탄소 경로 모형을 활용한 2050년 한국의 온실가스 감축 시나리오 비교 분석)

  • Park, Nyun-Bae;Yoo, Jung-Hwa;Jo, Mi-Hyun;Yun, Seong-Gwon;Jeon, Eui Chan
    • Journal of Korean Society for Atmospheric Environment
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    • v.28 no.5
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    • pp.556-570
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    • 2012
  • The Low Carbon Path Calculator is an excel-based model to project greenhouse gas emissions from 2009 to 2050, which is based on the 2050 Pathways Calculator developed by the UK Department of Energy and Climate Change (DECC). Scenarios are developed to reduce GHG emissions in Korea at 50% based on 2005 levels by 2050 using a Low Carbon Path Calculator. They were classified in four different cases, which are high renewable, high nuclear, high CCS and mixed option scenarios. The objectives of this study are to compare scenarios in terms of GHG emissions, final energy, primary energy and electricity generation and examine the usefulness of that model in terms of identifying pathways towards a low carbon emission society. This model will enhance the understanding of the pathways toward a low carbon society and the level of the climate change policy for policy makers, stakeholders, and the public. This study can be considered as a reference for developing strategies in reducing GHG emissions in the long term.