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      The Opisthorchis viverrini genome provides insights into life in the bile duct

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          Abstract

          Opisthorchiasis is a neglected, tropical disease caused by the carcinogenic Asian liver fluke, Opisthorchis viverrini. This hepatobiliary disease is linked to malignant cancer (cholangiocarcinoma, CCA) and affects millions of people in Asia. No vaccine is available, and only one drug (praziquantel) is used against the parasite. Little is known about O. viverrini biology and the diseases that it causes. Here we characterize the draft genome (634.5 Mb) and transcriptomes of O. viverrini, elucidate how this fluke survives in the hostile environment within the bile duct and show that metabolic pathways in the parasite are highly adapted to a lipid-rich diet from bile and/or cholangiocytes. We also provide additional evidence that O. viverrini and other flukes secrete proteins that directly modulate host cell proliferation. Our molecular resources now underpin profound explorations of opisthorchiasis/CCA and the design of new interventions.

          Abstract

          The Asian liver fluke is a parasitic worm that is linked to an increased risk of malignant cancer. Here, the authors sequence the draft genome and transcriptome of this fluke and provide insight into how the species has adapted to be able to survive in the bile duct.

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          Most cited references48

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          Transcription factors: from enhancer binding to developmental control.

          Developmental progression is driven by specific spatiotemporal domains of gene expression, which give rise to stereotypically patterned embryos even in the presence of environmental and genetic variation. Views of how transcription factors regulate gene expression are changing owing to recent genome-wide studies of transcription factor binding and RNA expression. Such studies reveal patterns that, at first glance, seem to contrast with the robustness of the developmental processes they encode. Here, we review our current knowledge of transcription factor function from genomic and genetic studies and discuss how different strategies, including extensive cooperative regulation (both direct and indirect), progressive priming of regulatory elements, and the integration of activities from multiple enhancers, confer specificity and robustness to transcriptional regulation during development.
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            The Schistosoma japonicum genome reveals features of host-parasite interplay.

            (2009)
            Schistosoma japonicum is a parasitic flatworm that causes human schistosomiasis, which is a significant cause of morbidity in China and the Philippines. Here we present a draft genomic sequence for the worm. The genome provides a global insight into the molecular architecture and host interaction of this complex metazoan pathogen, revealing that it can exploit host nutrients, neuroendocrine hormones and signalling pathways for growth, development and maturation. Having a complex nervous system and a well-developed sensory system, S. japonicum can accept stimulation of the corresponding ligands as a physiological response to different environments, such as fresh water or the tissues of its intermediate and mammalian hosts. Numerous proteases, including cercarial elastase, are implicated in mammalian skin penetration and haemoglobin degradation. The genomic information will serve as a valuable platform to facilitate development of new interventions for schistosomiasis control.
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              The ubiquitin-proteasome pathway: on protein death and cell life.

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                Author and article information

                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Pub. Group
                2041-1723
                09 July 2014
                : 5
                : 4378
                Affiliations
                [1 ]Faculty of Veterinary Science, The University of Melbourne, Melbourne , Victoria 3010, Australia
                [2 ]Genome Institute of Singapore , 60 Biopolis Street, Singapore 138672, Republic of Singapore
                [3 ]Department of Biology, University of Utah , Salt Lake City, Utah 84112, USA
                [4 ]Liver Fluke and Cholangiocarcinoma Research Center, Department of Biochemistry, Faculty of Medicine, Khon Kaen University , Khon Kaen 40002, Thailand
                [5 ]NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore , Singapore 138672, Republic of Singapore
                [6 ]Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School , Singapore 138672, Republic of Singapore
                [7 ]Research and Diagnostic Center for Emerging Infectious Diseases, Department of Parasitology, Faculty of Medicine, Khon Kaen University , Khon Kaen 40002, Thailand
                [8 ]BGI, Shenzhen 518083, China
                [9 ]Structural Chemistry Program, Eskitis Institute, Griffith University , Brisbane, Queensland 4111, Australia
                [10 ]Division of Biology, HHMI, California Institute of Technology , Pasadena, California 91125, USA
                [11 ]Department of Biology, University of Copenhagen , Copenhagen 2200, Denmark
                [12 ]Princess Al Jawhara Center of Excellence in the Research of Hereditary Disorders, King Abdulaziz University , Jeddah 21589, Saudi Arabia
                [13 ]Macau University of Science and Technology, Avenida Wai long , Taipa, Macau 999078, China
                [14 ]These authors are equal first authors
                Author notes
                Article
                ncomms5378
                10.1038/ncomms5378
                4104445
                25007141
                b2ec38b3-4904-4d43-993b-190e8ebb6ab9
                Copyright © 2014, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.

                This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/

                History
                : 03 March 2014
                : 11 June 2014
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