• Title/Summary/Keyword: Discovery DNA

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Genetic Risk Prediction for Normal-Karyotype Acute Myeloid Leukemia Using Whole-Exome Sequencing

  • Heo, Seong Gu;Hong, Eun Pyo;Park, Ji Wan
    • Genomics & Informatics
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    • v.11 no.1
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    • pp.46-51
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    • 2013
  • Normal-karyotype acute myeloid leukemia (NK-AML) is a highly malignant and cytogenetically heterogeneous hematologic cancer. We searched for somatic mutations from 10 pairs of tumor and normal cells by using a highly efficient and reliable analysis workflow for whole-exome sequencing data and performed association tests between the NK-AML and somatic mutations. We identified 21 nonsynonymous single nucleotide variants (SNVs) located in a coding region of 18 genes. Among them, the SNVs of three leukemia-related genes (MUC4, CNTNAP2, and GNAS) reported in previous studies were replicated in this study. We conducted stepwise genetic risk score (GRS) models composed of the NK-AML susceptible variants and evaluated the prediction accuracy of each GRS model by computing the area under the receiver operating characteristic curve (AUC). The GRS model that was composed of five SNVs (rs75156964, rs56213454, rs6604516, rs10888338, and rs2443878) showed 100% prediction accuracy, and the combined effect of the three reported genes was validated in the current study (AUC, 0.98; 95% confidence interval, 0.92 to 1.00). Further study with large sample sizes is warranted to validate the combined effect of these somatic point mutations, and the discovery of novel markers may provide an opportunity to develop novel diagnostic and therapeutic targets for NK-AML.

Comparison of Conditions for Cell Death-Inducing Agents Using a High Throughput-Compatible Nuclear Staining Assay (핵 염색을 이용한 세포사멸 유도물질 스크리닝의 조건 비교)

  • Lee, Sang-Han
    • Journal of Life Science
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    • v.18 no.9
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    • pp.1312-1315
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    • 2008
  • High throughput-drug screening plays a pivotal role for early stage of drug discovery process. In the course of assay development for screening of cell death-inducing agents, a protocol that is simple, time-saving, and high throughput-compatible was designed which was confirmed that the protocol can be worked by a HTS-compatible machine. In 96-well format, PC-3 cancer cells (1${\times}10^{4}$ cells/ml) were cultured for 24 hr. After 24 h-incubation with various medicinal plants extracts, the cells were then stained with DAPI for 30 min. The fluorescence intensity of the stained cells was measured semi-automatically with a multilabel counter. To test whether the present assay system effectively works, we screened about 850 medicinal plant extracts, and selected 1 positive crude extracts that contained cell death-inducing activity. These results suggest that the protocol is highly amenable to HTS implementation for a cell death-inducing agent(s).

Genetic Distances between Two Echiuran Populations Discriminated by PCR

  • Yoon, Jong-Man
    • Development and Reproduction
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    • v.23 no.4
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    • pp.377-384
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    • 2019
  • Genomic DNA extracted from representatives of two populations, Gunsan and Chinese, of Urechis spp. was amplified using PCR with several primers. The band-sharing (BS) value between individuals no. 05 from the Gunsan population and no. 22 from the Chinese population was 0.206, which was the lowest recognized value. Oligonucleotides primer OPC-04 revealed 44 unique loci, which distinguished the Chinese population. Primer OPB-17 allowed the discovery of 22 loci shared by the two populations, which were present in all samples. Based on the average BS results, individuals from the Gunsan population demonstrated lower BS values (0.661±0.012) than did those from the Chinese population (0.788±0.014; p<0.05). The shortest genetic distance (GD) displaying a noteworthy molecular difference was between individuals CHINESE no. 12 and no. 13 (GD=0.027). Individual no. 06 from the Gunsan population was most distantly related to CHINESE no. 22 (GD=0.703). A group tree of the two populations was constructed by UPGMA Euclidean GD analysis based on a total of 543 fragments generated using six primers. The explicit markers recognized in this study will be used for genetic analysis, as well as to evaluate the species security and proliferation of echiuran individuals in intertidal regions of the Korean Peninsula.

Discovery of Two New Talaromyces Species from Crop Field Soil in Korea

  • Adhikari, Mahesh;Yadav, Dil Raj;Kim, Sangwoo;Um, Yong Hyun;Kim, Hyung Seung;Lee, Hyang Burm;Lee, Youn Su
    • Mycobiology
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    • v.43 no.4
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    • pp.402-407
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    • 2015
  • Two new fungal species of the genus Talaromyces, Talaromyces purpurogenus and Talaromyces trachyspermus from the Trichocomaceae family, were recovered during an investigation of fungal communities in soil collected from the Gangwon-do and Jeollanam-do provinces of Korea. These two species have not been previously officially reported from Korea. In this study, detailed descriptions of internal transcribed spacer rDNA and beta-tubulin gene regions of these two fungi are presented. Morphological features of the two fungi in five agar media, potato dextrose, oatmeal, malt extract, czapek yeast extract, and yeast extract sucrose, are also reported. The species were identified on the basis of molecular and morphological analysis, and herein we present data with detailed descriptions and figures.

hpvPDB: An Online Proteome Reserve for Human Papillomavirus

  • Kumar, Satish;Jena, Lingaraja;Daf, Sangeeta;Mohod, Kanchan;Goyal, Peyush;Varma, Ashok K.
    • Genomics & Informatics
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    • v.11 no.4
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    • pp.289-291
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    • 2013
  • Human papillomavirus (HPV) infection is the leading cause of cancer mortality among women worldwide. The molecular understanding of HPV proteins has significant connotation for understanding their intrusion in the host and designing novel protein vaccines and anti-viral agents, etc. Genomic, proteomic, structural, and disease-related information on HPV is available on the web; yet, with trivial annotations and more so, it is not well customized for data analysis, host-pathogen interaction, strain-disease association, drug designing, and sequence analysis, etc. We attempted to design an online reserve with comprehensive information on HPV for the end users desiring the same. The Human Papillomavirus Proteome Database (hpvPDB) domiciles proteomic and genomic information on 150 HPV strains sequenced to date. Simultaneous easy expandability and retrieval of the strain-specific data, with a provision for sequence analysis and exploration potential of predicted structures, and easy access for curation and annotation through a range of search options at one platform are a few of its important features. Affluent information in this reserve could be of help for researchers involved in structural virology, cancer research, drug discovery, and vaccine design.

Alsidium oliveiranum sp. nov. (Rhodomelaceae, Rhodophyta), an overlooked species from the southwestern Atlantic based on morphology and DNA sequence data

  • Guimaraes, Silvia M.P.B.;Soares, Luanda Pereira;Fujii, Mutue Toyota;Diaz-Tapia, Pilar
    • ALGAE
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    • v.34 no.3
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    • pp.187-198
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    • 2019
  • The exploration of seaweed diversity in poorly studied habitats has often led to the discovery of new species. Sand-covered rocks are an example, as they received less attention than sand-free rocky intertidal habitats during seaweed diversity surveys in Brazil. In sand-covered rocks from Espirito Santo and Rio de Janeiro we found an alga whose morphology was unique among rhodomelacean species previously reported in Brazil. With the aim to clarify the taxonomic identity of this species we studied its morphology, as well as its phylogenetic relationships. Molecular analyses resolved this species in the genus Alsidium (tribe Alsidieae) and differed from sequenced congeners with divergences ${\geq}2.5$ and 4.2% in the rbcL and cox1 genes, respectively. Morphological characters were in agreement with the genus Alsidium, and differed from other species currently recognized in the genus. The species consisted of a basal crust and scarcely branched erect axes with seven pericentral cells covered by a continuous layer of cortical cells. Reproductive structures were formed on clusters of short determinate branches. Therefore, the new species A. oliveiranum is proposed based on morphological and molecular evidence. Our findings contribute to better understand the diversity of the tribe Alsidieae, which is particularly diverse in the Americas.

Role of Pentacyclic Triterpenoids in Chemoprevention and Anticancer Treatment: An Overview on Targets and Underling Mechanisms

  • Ghante, Mahavir H.;Jamkhande, Prasad G.
    • Journal of Pharmacopuncture
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    • v.22 no.2
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    • pp.55-67
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    • 2019
  • The incidences of cancer are continuously increasing worldwide, affecting life of millions of people. Several factors associated with the internal and external environment are responsible for this deadly disease. The key internal determinants like abnormal hormonal regulation, genetic mutations and external determinants such as lifestyle and occupational factors enhances onset of cancer. From the ancient time, plants were remained as the most trusted source of medicine for the treatment of diverse disease conditions. Extensive studies have been performed for the discovery of effective anticancer agent from the plant and still it is going on. Pentacyclic triterpenoids are biologically active phytochemicals having a different range of activities such as anti-inflammatory, hepatoprotective, anti-hypertensive, antiulcerogenic and anti-tumor. These compounds generally contain ursane, oleanane, lupane and friedelane as a chief skeleton of pentacyclic triterpenoids which are generally present in higher plants. Isoprene unit, phytochemical, with good antitumor/anticancer activity is required for the biosynthesis of pentacyclic triterpenoids. Mechanisms such as cytotoxicity, DNA polymerase inhibition, regulation of apoptosis, change in signal transductions, interfere with angiogenesis and dedifferentiation, antiproliferative activity and metastasis inhibition are might be responsible for their anticancer effect. Present review spotlights diverse targets, mechanisms and pathways of pentacyclic triterpenoids responsible for anticancer effect.

Bioprospecting of Novel and Bioactive Metabolites from Endophytic Fungi Isolated from Rubber Tree Ficus elastica Leaves

  • Ding, Zhuang;Tao, Tao;Wang, Lili;Zhao, Yanna;Huang, Huiming;Zhang, Demeng;Liu, Min;Wang, Zhengping;Han, Jun
    • Journal of Microbiology and Biotechnology
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    • v.29 no.5
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    • pp.731-738
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    • 2019
  • Endophytic fungi are an important component of plant microbiota, and have the excellent capacity for producing a broad variety of bioactive metabolites. These bioactive metabolites not only affect the survival of the host plant, but also provide valuable lead compounds for novel drug discovery. In this study, forty-two endophytic filamentous fungi were isolated from Ficus elastica leaves, and further identified as seven individual taxa by ITS-rDNA sequencing. The antimicrobial activity of these endophytic fungi was evaluated against five pathogenic microorganisms. Two strains, Fes1711 (Penicillium funiculosum) and Fes1712 (Trichoderma harzianum), displayed broad-spectrum bioactivities. Our following study emphasizes the isolation, identification and bioactivity testing of chemical metabolites produced by T. harzianum Fes1712. Two new isocoumarin derivatives (1 and 2), together with three known compounds (3-5) were isolated, and their structures were elucidated using NMR and MS. Compounds 1 and 2 exhibited inhibitory activity against Escherichia coli. Our findings reveal that endophytic fungi from the rubber tree F. elastica leaves exhibit unique characteristics and are potential producers of novel natural bioactive products.

Synthetic Biology Tools for Novel Secondary Metabolite Discovery in Streptomyces

  • Lee, Namil;Hwang, Soonkyu;Lee, Yongjae;Cho, Suhyung;Palsson, Bernhard;Cho, Byung-Kwan
    • Journal of Microbiology and Biotechnology
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    • v.29 no.5
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    • pp.667-686
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    • 2019
  • Streptomyces are attractive microbial cell factories that have industrial capability to produce a wide array of bioactive secondary metabolites. However, the genetic potential of the Streptomyces species has not been fully utilized because most of their secondary metabolite biosynthetic gene clusters (SM-BGCs) are silent under laboratory culture conditions. In an effort to activate SM-BGCs encoded in Streptomyces genomes, synthetic biology has emerged as a robust strategy to understand, design, and engineer the biosynthetic capability of Streptomyces secondary metabolites. In this regard, diverse synthetic biology tools have been developed for Streptomyces species with technical advances in DNA synthesis, sequencing, and editing. Here, we review recent progress in the development of synthetic biology tools for the production of novel secondary metabolites in Streptomyces, including genomic elements and genome engineering tools for Streptomyces, the heterologous gene expression strategy of designed biosynthetic gene clusters in the Streptomyces chassis strain, and future directions to expand diversity of novel secondary metabolites.

Discovery of Cellular RhoA Functions by the Integrated Application of Gene Set Enrichment Analysis

  • Chun, Kwang-Hoon
    • Biomolecules & Therapeutics
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    • v.30 no.1
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    • pp.98-116
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    • 2022
  • The small GTPase RhoA has been studied extensively for its role in actin dynamics. In this study, multiple bioinformatics tools were applied cooperatively to the microarray dataset GSE64714 to explore previously unidentified functions of RhoA. Comparative gene expression analysis revealed 545 differentially expressed genes in RhoA-null cells versus controls. Gene set enrichment analysis (GSEA) was conducted with three gene set collections: (1) the hallmark, (2) the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and (3) the Gene Ontology Biological Process. GSEA results showed that RhoA is related strongly to diverse pathways: cell cycle/growth, DNA repair, metabolism, keratinization, response to fungus, and vesicular transport. These functions were verified by heatmap analysis, KEGG pathway diagramming, and direct acyclic graphing. The use of multiple gene set collections restricted the leakage of information extracted. However, gene sets from individual collections are heterogenous in gene element composition, number, and the contextual meaning embraced in names. Indeed, there was a limit to deriving functions with high accuracy and reliability simply from gene set names. The comparison of multiple gene set collections showed that although the gene sets had similar names, the gene elements were extremely heterogeneous. Thus, the type of collection chosen and the analytical context influence the interpretation of GSEA results. Nonetheless, the analyses of multiple collections made it possible to derive robust and consistent function identifications. This study confirmed several well-described roles of RhoA and revealed less explored functions, suggesting future research directions.