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  1. Article ; Online: Anti-Chikungunya Viral Activities of Aplysiatoxin-Related Compounds from the Marine Cyanobacterium Trichodesmium erythraeum

    Deepak Kumar Gupta / Parveen Kaur / See Ting Leong / Lik Tong Tan / Michèle R. Prinsep / Justin Jang Hann Chu

    Marine Drugs, Vol 12, Iss 1, Pp 115-

    2014  Volume 127

    Abstract: Tropical filamentous marine cyanobacteria have emerged as a viable source of novel bioactive natural products for drug discovery and development. In the present study, aplysiatoxin (1), debromoaplysiatoxin (2) and anhydrodebromoaplysiatoxin (3), as well ... ...

    Abstract Tropical filamentous marine cyanobacteria have emerged as a viable source of novel bioactive natural products for drug discovery and development. In the present study, aplysiatoxin (1), debromoaplysiatoxin (2) and anhydrodebromoaplysiatoxin (3), as well as two new analogues, 3-methoxyaplysiatoxin (4) and 3-methoxydebromoaplysiatoxin (5), are reported for the first time from the marine cyanobacterium Trichodesmium erythraeum. The identification of the bloom-forming cyanobacterial strain was confirmed based on phylogenetic analysis of its 16S rRNA sequences. Structural determination of the new analogues was achieved by extensive NMR spectroscopic analysis and comparison with NMR spectral data of known compounds. In addition, the antiviral activities of these marine toxins were assessed using Chikungunya virus (CHIKV)-infected cells. Post-treatment experiments using the debrominated analogues, namely compounds 2, 3 and 5, displayed dose-dependent inhibition of CHIKV when tested at concentrations ranging from 0.1 µM to 10.0 µM. Furthermore, debromoaplysiatoxin (2) and 3-methoxydebromoaplysiatoxin (5) exhibited significant anti-CHIKV activities with EC50 values of 1.3 μM and 2.7 μM, respectively, and selectivity indices of 10.9 and 9.2, respectively.
    Keywords marine cyanobacterium ; Trichodesmium erythraeum ; aplysiatoxin ; antiviral ; Chikungunya virus ; Biology (General) ; QH301-705.5
    Subject code 540
    Language English
    Publishing date 2014-01-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Long span DNA paired-end-tag (DNA-PET) sequencing strategy for the interrogation of genomic structural mutations and fusion-point-guided reconstruction of amplicons.

    Fei Yao / Pramila N Ariyaratne / Axel M Hillmer / Wah Heng Lee / Guoliang Li / Audrey S M Teo / Xing Yi Woo / Zhenshui Zhang / Jieqi P Chen / Wan Ting Poh / Kelson F B Zawack / Chee Seng Chan / See Ting Leong / Say Chuan Neo / Poh Sum D Choi / Song Gao / Niranjan Nagarajan / Hervé Thoreau / Atif Shahab /
    Xiaoan Ruan / Valère Cacheux-Rataboul / Chia-Lin Wei / Guillaume Bourque / Wing-Kin Sung / Edison T Liu / Yijun Ruan

    PLoS ONE, Vol 7, Iss 9, p e

    2012  Volume 46152

    Abstract: Structural variations (SVs) contribute significantly to the variability of the human genome and extensive genomic rearrangements are a hallmark of cancer. While genomic DNA paired-end-tag (DNA-PET) sequencing is an attractive approach to identify genomic ...

    Abstract Structural variations (SVs) contribute significantly to the variability of the human genome and extensive genomic rearrangements are a hallmark of cancer. While genomic DNA paired-end-tag (DNA-PET) sequencing is an attractive approach to identify genomic SVs, the current application of PET sequencing with short insert size DNA can be insufficient for the comprehensive mapping of SVs in low complexity and repeat-rich genomic regions. We employed a recently developed procedure to generate PET sequencing data using large DNA inserts of 10-20 kb and compared their characteristics with short insert (1 kb) libraries for their ability to identify SVs. Our results suggest that although short insert libraries bear an advantage in identifying small deletions, they do not provide significantly better breakpoint resolution. In contrast, large inserts are superior to short inserts in providing higher physical genome coverage for the same sequencing cost and achieve greater sensitivity, in practice, for the identification of several classes of SVs, such as copy number neutral and complex events. Furthermore, our results confirm that large insert libraries allow for the identification of SVs within repetitive sequences, which cannot be spanned by short inserts. This provides a key advantage in studying rearrangements in cancer, and we show how it can be used in a fusion-point-guided-concatenation algorithm to study focally amplified regions in cancer.
    Keywords Medicine ; R ; Science ; Q
    Subject code 612
    Language English
    Publishing date 2012-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Recurrent Fusion Genes in Gastric Cancer

    Fei Yao / Jaya P. Kausalya / Yee Yen Sia / Audrey S.M. Teo / Wah Heng Lee / Alicia G.M. Ong / Zhenshui Zhang / Joanna H.J. Tan / Guoliang Li / Denis Bertrand / Xingliang Liu / Huay Mei Poh / Peiyong Guan / Feng Zhu / Thushangi Nadeera Pathiraja / Pramila N. Ariyaratne / Jaideepraj Rao / Xing Yi Woo / Shaojiang Cai /
    Fabianus H. Mulawadi / Wan Ting Poh / Lavanya Veeravalli / Chee Seng Chan / Seong Soo Lim / See Ting Leong / Say Chuan Neo / Poh Sum D. Choi / Elaine G.Y. Chew / Niranjan Nagarajan / Pierre-Étienne Jacques / Jimmy B.Y. So / Xiaoan Ruan / Khay Guan Yeoh / Patrick Tan / Wing-Kin Sung / Walter Hunziker / Yijun Ruan / Axel M. Hillmer

    Cell Reports, Vol 12, Iss 2, Pp 272-

    CLDN18-ARHGAP26 Induces Loss of Epithelial Integrity

    2015  Volume 285

    Abstract: Genome rearrangements, a hallmark of cancer, can result in gene fusions with oncogenic properties. Using DNA paired-end-tag (DNA-PET) whole-genome sequencing, we analyzed 15 gastric cancers (GCs) from Southeast Asians. Rearrangements were enriched in ... ...

    Abstract Genome rearrangements, a hallmark of cancer, can result in gene fusions with oncogenic properties. Using DNA paired-end-tag (DNA-PET) whole-genome sequencing, we analyzed 15 gastric cancers (GCs) from Southeast Asians. Rearrangements were enriched in open chromatin and shaped by chromatin structure. We identified seven rearrangement hot spots and 136 gene fusions. In three out of 100 GC cases, we found recurrent fusions between CLDN18, a tight junction gene, and ARHGAP26, a gene encoding a RHOA inhibitor. Epithelial cell lines expressing CLDN18-ARHGAP26 displayed a dramatic loss of epithelial phenotype and long protrusions indicative of epithelial-mesenchymal transition (EMT). Fusion-positive cell lines showed impaired barrier properties, reduced cell-cell and cell-extracellular matrix adhesion, retarded wound healing, and inhibition of RHOA. Gain of invasion was seen in cancer cell lines expressing the fusion. Thus, CLDN18-ARHGAP26 mediates epithelial disintegration, possibly leading to stomach H+ leakage, and the fusion might contribute to invasiveness once a cell is transformed.
    Keywords Science ; Q ; Biology (General) ; QH301-705.5
    Publishing date 2015-07-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Recurrent Fusion Genes in Gastric Cancer

    Fei Yao / Jaya P. Kausalya / Yee Yen Sia / Audrey S.M. Teo / Wah Heng Lee / Alicia G.M. Ong / Zhenshui Zhang / Joanna H.J. Tan / Guoliang Li / Denis Bertrand / Xingliang Liu / Huay Mei Poh / Peiyong Guan / Feng Zhu / Thushangi Nadeera Pathiraja / Pramila N. Ariyaratne / Jaideepraj Rao / Xing Yi Woo / Shaojiang Cai /
    Fabianus H. Mulawadi / Wan Ting Poh / Lavanya Veeravalli / Chee Seng Chan / Seong Soo Lim / See Ting Leong / Say Chuan Neo / Poh Sum D. Choi / Elaine G.Y. Chew / Niranjan Nagarajan / Pierre-Étienne Jacques / Jimmy B.Y. So / Xiaoan Ruan / Khay Guan Yeoh / Patrick Tan / Wing-Kin Sung / Walter Hunziker / Yijun Ruan / Axel M. Hillmer

    Cell Reports, Vol 12, Iss 2, Pp 272-

    CLDN18-ARHGAP26 Induces Loss of Epithelial Integrity

    2015  Volume 285

    Abstract: Genome rearrangements, a hallmark of cancer, can result in gene fusions with oncogenic properties. Using DNA paired-end-tag (DNA-PET) whole-genome sequencing, we analyzed 15 gastric cancers (GCs) from Southeast Asians. Rearrangements were enriched in ... ...

    Abstract Genome rearrangements, a hallmark of cancer, can result in gene fusions with oncogenic properties. Using DNA paired-end-tag (DNA-PET) whole-genome sequencing, we analyzed 15 gastric cancers (GCs) from Southeast Asians. Rearrangements were enriched in open chromatin and shaped by chromatin structure. We identified seven rearrangement hot spots and 136 gene fusions. In three out of 100 GC cases, we found recurrent fusions between CLDN18, a tight junction gene, and ARHGAP26, a gene encoding a RHOA inhibitor. Epithelial cell lines expressing CLDN18-ARHGAP26 displayed a dramatic loss of epithelial phenotype and long protrusions indicative of epithelial-mesenchymal transition (EMT). Fusion-positive cell lines showed impaired barrier properties, reduced cell-cell and cell-extracellular matrix adhesion, retarded wound healing, and inhibition of RHOA. Gain of invasion was seen in cancer cell lines expressing the fusion. Thus, CLDN18-ARHGAP26 mediates epithelial disintegration, possibly leading to stomach H+ leakage, and the fusion might contribute to invasiveness once a cell is transformed.
    Keywords Biology (General) ; QH301-705.5
    Language English
    Publishing date 2015-07-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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