• Title/Summary/Keyword: related genes

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Identification of p54nrb and the 14-3-3 Protein HS1 as TNF-α-Inducible Genes Related to Cell Cycle Control and Apoptosis in Human Arterial Endothelial Cells

  • Stier, Sebastian;Totzke, Gudrun;Grunewald, Elisabeth;Neuhaus, Thomas;Fronhoffs, Stefan;Schoneborn, Silke;Vetter, Hans;Ko, Yon
    • BMB Reports
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    • v.38 no.4
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    • pp.447-456
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    • 2005
  • TNF-$\alpha$ plays a pivotal role in inflammation processes which are mainly regulated by endothelial cells. While TNF-$\alpha$ induces apoptosis of several cell types like tumor cells, endothelial cells are resistant to TNFa mediated cell death. The cytotoxic effects of TNF-$\alpha$ on most cells are only evident if RNA or protein synthesis is inhibited, suggesting that de novo RNA or protein synthesis protect cells from TNF-$\alpha$ cytotoxicity, presumably by NF-${\kappa}B$ mediated induction of protective genes. However, the cytoprotective genes involved in NF-${\kappa}B$ dependent endothelial cell survival have not been sufficiently identified. In the present study, the suppression subtractive hybridization (SSH) method was employed to identify rarely transcribed TNF-$\alpha$ inducible genes in human arterial endothelial cells related to cell survival and cell cycle. The TNF-$\alpha$-induced expression of the RNA binding protein $p54^{nrb}$ and the 14-3-3 protein HS1 as shown here for the first time may contribute to the TNF-$\alpha$ mediated cell protection of endothelial cells. These genes have been shown to play pivotal roles in cell survival and cell cycle control in different experimental settings. The concerted expression of these genes together with other genes related to cell protection and cell cycle like DnaJ, $p21^{cip1}$ and the ubiquitin activating enzyme E1 demonstrates the identification of new genes in the context of TNF-$\alpha$ induced gene expression patterns mediating the prosurvival effect of TNF-$\alpha$ in endothelial cells.

Safety Assessment of Lactiplantibacillus (formerly Lactobacillus) plantarum Q180

  • Kwon, Yoo Jin;Chun, Byung Hee;Jung, Hye Su;Chu, Jaeryang;Joung, Hyunchae;Park, Sung Yurb;Kim, Byoung Kook;Jeon, Che Ok
    • Journal of Microbiology and Biotechnology
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    • v.31 no.10
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    • pp.1420-1429
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    • 2021
  • The safety of the probiotic strain Q180, which exerts postprandial lipid-lowering effects, was bioinformatically and phenotypically evaluated. The genome of strain Q180 was completely sequenced, and single circular chromosome of 3,197,263 bp without any plasmid was generated. Phylogenetic and related analyses using16S rRNA gene and whole-genome sequences revealed that strain Q180 is a member of Lactiplantibacillus (Lp., formerly Lactobacillus) plantarum. Antimicrobial resistance (AMR) genes were bioinformatically analyzed using all Lp. plantarum genomes available in GenBank, which showed that AMR genes are present differently depending on Lp. plantarum strains. Bioinformatic analysis demonstrated that some mobile genetic elements such as prophages and insertion sequences were identified in the genome of strain Q180, but because they did not contain harmful genes such as AMR genes and virulence factor (VF)- and toxin-related genes, it was suggested that there is no transferability of harmful genes. The minimum inhibition concentrations of seven tested antibiotics suggested by the European Food Safety Authority guidelines were slightly lower than or equal to the microbiological cut-off values for Lp. plantarum. Strain Q180 did not show hemolytic and gelatinase activities and biogenic amine-producing ability. Taken together, this study demonstrated the safety of strain Q180 in terms of absence of AMR genes and VF- and toxin-related genes as a probiotic strain.

An EST survey of genes expressed in liver of rock bream(Oplegnathus fasciatus) with particular interests on the stress-responsive and immune-related genes

  • Park, Byul-Nim;Park, Ji-Eun;Kim, Ki-Hong;Kim, Dong-Soo;Nam, Yoon-Kwon
    • Proceedings of the Korean Aquaculture Society Conference
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    • 2003.10a
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    • pp.43-43
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    • 2003
  • EST analysis was performed to identify stress-responsive and immune-related genes from rock bream (Oplegnathus fasciatus). cDNA libraries were constructed with liver and randomly chosen 624 clones were subjected to automated sequence analysis. Of 624 clones sequenced in total, approximately 15% of ESTs was novel sequences (no match to GenBank) or sequences with high homology to hypothetical/unknown genes. The bioinforamtic sequence analysis including functional clustering, homology grouping, contig assembly with electronic northern and organism matches were carried out. Several potential stress-responsive biomarker and/or immune-related genes were identified in all the tissues examined. It included lectins, ferritins, CP450, proteinase, proteinase inhibitors, anti-oxidant enzymes, various heat-shock proteins, warm temperature acclimation protein, complements, methyltransferase, zinc finger proteins, lysozymes, macrophage maturation associated protein, and others. This information will offer new possibilities as fundamental baseline data for understanding and addressing their molecular mechanism involved in host defense and immune systems of this species.

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Toxicogenomic Study to Identify Potential New Mechanistic Markers on Direct-Acting Mutagens in Human Hepatocytes (THLE-3)

  • Kim, Youn-Jung;Song, Mi-Kyung;Song, Mee;Ryu, Jae-Chun
    • Molecular & Cellular Toxicology
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    • v.3 no.4
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    • pp.231-237
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    • 2007
  • Exposure to DNA-damaging agents can elicit a variety of stress-related responses that may alter the expression of genes associated with numerous biological pathways. We used 19 k whole human genome chip to detect gene expression profiles and potential signature genes in human normal hepatocytes (THLE-3) by treatment of five direct acting mutagens, furylfuramide (AF-2), N-nitroso-N-methylurea (MNU), methylmethanesulfonate (MMS), 4-nitroquinoline-N-oxide (4-NQO) and 2-nitrofluorene (2NF) of the $IC_{20}$ concentration for 3 h. Fifty one up-regulated common genes and 45 down-regulated common genes above 1.5-fold by five direct-acting mutagens were identified by clustering analysis. Many of these changed genes have some association with apoptosis, control of cell cycle, regulation of transcription and signal transduction. Genes related to these functions, as TP73L, E2F5, MST016, SOX5, MAFB, LIF, SII3, TFIIS, EMR1, CYTL1, CX3CR1 and RHOH are up-regulated. Down-regulated genes are ALOX15B, xs155, IFITM1, BATF, VAV2, CD79A, DCDC2, TNFSF8 and KOX8. We suggest that gene expression profiling on mutagens by toxicogenomic analysis affords promising opportunities to reveal potential new mechanistic markers of genotoxicity.

Screening of Novel Inducible Resistance Gene to Macrolide-Lincosamide-Streptogramin B (MLS) Antibiotics from Clinical Isolates of Staphylococcus spp (임상분리 Staphylococcus속 균주로부터 마크로라이드-린코사마이드-스트렙토그라민 B(MLS)계 항생물질에 대한 새로운 유도내성 유전자의 검색)

  • 오정자;권애란;이미정;김숙경;최성숙;최응칠;김병각
    • Biomolecules & Therapeutics
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    • v.1 no.2
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    • pp.177-182
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    • 1993
  • From 84 clinical isolates of Staphylococcus species, ten strains showing inducible resistance to MLS antibiotics were selected by disk agar diffusion method. Colony hybridization was executed using two MLS inducible resistance genes, ermA and ermC, previously identified from S. aureus as probes. S. hemolyticus 401 and S. epidermidis 542 whose genes were not homologous to those probes were finally selected. It was determined that the resistance genes of S. hemolyticus 401 and S. epidermidis 542 were not homologous to ermA, ermC and ermAM by Southern hybridization. S. epidermidis 542 had a plasmid DNA. To know if the plasmid may have genes related to inducible resistance, it was attempted to transform B. subtilis BR151 and S. aureus RN4220 with the plasmid prepared from S. epidermidis 542. It was shown that the gene related to inducible resistance to MLS antibiotics did not exist in this plasmid. These results indicate that two clinical isolates of S. hemolyticus 401 and S. epidermidis 542 had novel genes which were not homologous to MLS resistance genes identified previously. It was assumed that these genes may exist in chromosomal DNA.

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Identification and molecular characterization of doublesex and mab-3-related transcription factor(dmrt) in brackish water flea, Diaphanosoma celebensis, exposed to bisphenol analogs

  • Cho, Hayoung;Jeon, Min Jeong;Lee, Young-Mi
    • Korean Journal of Environmental Biology
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    • v.39 no.2
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    • pp.160-168
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    • 2021
  • Doublesex and mab-3 related transcription factor(dmrt) play crucial roles in sex determination and sex differentiation in vertebrates and invertebrates. Although dmrt genes have been identified in vertebrates, little is known about aquatic invertebrates. In this study, two dmrt genes, namely, Dc_dmrt93B and Dc_dmrt99B, were identified from brackish water flea, Diaphanosoma celebensis. Transcriptional changes were observed in the dmrt genes when the flea was exposed to bisphenol(BP), an endocrine disruptor. Sequence and phylogenetic analyses showed that both dmrt genes contained two conserved domains, namely, DM and DMA, closely clustered with those of Daphnia spp. Additionally, a significant increase in the Dc_dmrt99B mRNA expression level was observed upon exposure to intermediate concentrations of BP (bisphenol A>bisphenol S=bisphenol F, p<0.05), while the expression of Dc_dmrt93B mRNA was slightly modulated. These findings imply that the two dmrt genes may be involved in sex differentiation of D. celebensis. Furthermore, it was found that the ability of BP to modulate dmrt genes could affect development and reproduction. This study provides a basis for understanding the function of the dmrt genes and the molecular mode of action of BP in small crustaceans.

Identification of key genes and functional enrichment analysis of liver fibrosis in nonalcoholic fatty liver disease through weighted gene co-expression network analysis

  • Yue Hu;Jun Zhou
    • Genomics & Informatics
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    • v.21 no.4
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    • pp.45.1-45.11
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    • 2023
  • Nonalcoholic fatty liver disease (NAFLD) is a common type of chronic liver disease, with severity levels ranging from nonalcoholic fatty liver to nonalcoholic steatohepatitis (NASH). The extent of liver fibrosis indicates the severity of NASH and the risk of liver cancer. However, the mechanism underlying NASH development, which is important for early screening and intervention, remains unclear. Weighted gene co-expression network analysis (WGCNA) is a useful method for identifying hub genes and screening specific targets for diseases. In this study, we utilized an mRNA dataset of the liver tissues of patients with NASH and conducted WGCNA for various stages of liver fibrosis. Subsequently, we employed two additional mRNA datasets for validation purposes. Gene set enrichment analysis (GSEA) was conducted to analyze gene function enrichment. Through WGCNA and subsequent analyses, complemented by validation using two additional datasets, we identified five genes (BICC1, C7, EFEMP1, LUM, and STMN2) as hub genes. GSEA analysis indicated that gene sets associated with liver metabolism and cholesterol homeostasis were uniformly downregulated. BICC1, C7, EFEMP1, LUM, and STMN2 were identified as hub genes of NASH, and were all related to liver metabolism, NAFLD, NASH, and related diseases. These hub genes might serve as potential targets for the early screening and treatment of NASH.

Cadmium chloride down-regulates the expression of Rad51 in HC11 cells and reduces knock-in efficiency

  • Ga-Yeon Kim;Man-Jong Kang
    • Journal of Animal Reproduction and Biotechnology
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    • v.38 no.3
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    • pp.99-108
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    • 2023
  • Background: Efficient gene editing technology is needed for successful knock-in. Homologous recombination (HR) is a major double-strand break repair pathway that can be utilized for accurately inserting foreign genes into the genome. HR occurs during the S/G2 phase, and the DNA mismatch repair (MMR) pathway is inextricably linked to HR to maintain HR fidelity. This study was conducted to investigate the effect of inhibiting MMR-related genes using CdCl2, an MMR-related gene inhibitor, on HR efficiency in HC11 cells. Methods: The mRNA and protein expression levels of MMR-related genes (Msh2, Msh3, Msh6, Mlh1, Pms2), the HR-related gene Rad51, and the NHEJ-related gene DNA Ligase IV were assessed in HC11 cells treated with 10 μM of CdCl2 for 48 hours. In addition, HC11 cells were transfected with a CRISPR/sgRNA expression vector and a knock-in vector targeting Exon3 of the mouse-beta casein locus, and treated with 10 μM cadmium for 48 hours. The knock-in efficiency was monitored through PCR. Results: The treatment of HC11 cells with a high-dose of CdCl2 decreased the mRNA expression of the HR-related gene Rad51 in HC11 cells. In addition, the inhibition of MMR-related genes through CdCl2 treatment did not lead to an increase in knock-in efficiency. Conclusions: The inhibition of MMR-related gene expression through high-dose CdCl2 treatment reduces the expression of the HR-related gene Rad51, which is active during recombination. Therefore, it was determined that CdCl2 is an inappropriate compound for improving HR efficiency.

A Literature Study about the Correlation between Genetic Studies on Atopic Dermatitis, Sasang Constitution, and Sasang Constitional Study on Atopic Dermatitis (아토피 피부염에서 유전자 연구와 사상체질의학적 접근의 상관성에 관한 문헌적 고찰)

  • Son, Jung-Min;Choi, In-Hwa
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.18 no.2
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    • pp.1-9
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    • 2005
  • Objectives: The objective of this study is to investigate the correlation between genetic studies on atopic dermatitis. sasang constitution, and sasang constitional study on atopic dermatitis. Methods: We retrieved data on PubMed for the papers of genetic study on atopic dermatitis. And for the papers on genetic study of sasang constitution and sasang constitional study of atopic dermatitis, we referred to papers have reported on domestic medical journal and domestic korean medicine journal. And we investigated correlations among the studies. Results: 1. There are two studies on genetic study on atopic dermatitis. One has been performed to find out genes related to atopic dermatitis by case-control study. The other has been to investigate the correlation between atopic dermatitis and the genes their functions were well-known. 2. Gene study on sasang constitution was performed to observe the distribution of the genes which is related with characteristics of sasang constitution, but there was no significant maldistribution of the genes. 3. There was no correlation between genetic study on atopic dermatitis and genetic study on sasang constitution. Conclusion & Discussion: In the Sasang constitutional study of atopic dermatitis, it seems that further studies on genes related to characteristics of skin, character affecting on behavior, and neurobiological difference among Sasang constitution are required as well as studies on distribution of genes related atopic dermatitis.

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Inferring Disease-related Genes using Title and Body in Biomedical Text (생물학 문헌 데이터의 제목과 본문을 이용한 질병 관련 유전자 추론 방법)

  • Kim, Jeongwoo;Kim, Hyunjin;Yeo, Yunku;Shin, Mincheol;Park, Sanghyun
    • KIISE Transactions on Computing Practices
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    • v.23 no.1
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    • pp.28-36
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    • 2017
  • After the genome projects of the 90s, a vast number of gene studies have been stored in online databases. By using these databases, several biological relationships can be inferred. In this study, we proposed a method to infer disease-gene relationships using title and body in biomedical text. The title was used to extract hub genes from data in the literature; whereas, the body of the literature was used to extract sub genes that are related to hub genes. Through these steps, we were able to construct a local gene-network for each report in the literature. By integrating the local gene-networks, we then constructed a global gene-network. Subsequent analyses of the global gene-network allowed inference of disease-related genes with high rank. We validated the proposed method by comparing with previous methods. The results indicated that the proposed method is a meaningful approach to infer disease-related genes.