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  • 1
    Publication Date: 2011-07-15
    Description: Malignant transformation, driven by gain-of-function mutations in oncogenes and loss-of-function mutations in tumour suppressor genes, results in cell deregulation that is frequently associated with enhanced cellular stress (for example, oxidative, replicative, metabolic and proteotoxic stress, and DNA damage). Adaptation to this stress phenotype is required for cancer cells to survive, and consequently cancer cells may become dependent upon non-oncogenes that do not ordinarily perform such a vital function in normal cells. Thus, targeting these non-oncogene dependencies in the context of a transformed genotype may result in a synthetic lethal interaction and the selective death of cancer cells. Here we used a cell-based small-molecule screening and quantitative proteomics approach that resulted in the unbiased identification of a small molecule that selectively kills cancer cells but not normal cells. Piperlongumine increases the level of reactive oxygen species (ROS) and apoptotic cell death in both cancer cells and normal cells engineered to have a cancer genotype, irrespective of p53 status, but it has little effect on either rapidly or slowly dividing primary normal cells. Significant antitumour effects are observed in piperlongumine-treated mouse xenograft tumour models, with no apparent toxicity in normal mice. Moreover, piperlongumine potently inhibits the growth of spontaneously formed malignant breast tumours and their associated metastases in mice. Our results demonstrate the ability of a small molecule to induce apoptosis selectively in cells that have a cancer genotype, by targeting a non-oncogene co-dependency acquired through the expression of the cancer genotype in response to transformation-induced oxidative stress.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3316487/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3316487/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Raj, Lakshmi -- Ide, Takao -- Gurkar, Aditi U -- Foley, Michael -- Schenone, Monica -- Li, Xiaoyu -- Tolliday, Nicola J -- Golub, Todd R -- Carr, Steven A -- Shamji, Alykhan F -- Stern, Andrew M -- Mandinova, Anna -- Schreiber, Stuart L -- Lee, Sam W -- 5 RC2 CA148399-02/CA/NCI NIH HHS/ -- CA080058/CA/NCI NIH HHS/ -- CA085681/CA/NCI NIH HHS/ -- CA127247/CA/NCI NIH HHS/ -- CA142805/CA/NCI NIH HHS/ -- P01 CA080058/CA/NCI NIH HHS/ -- P01 CA080058-02/CA/NCI NIH HHS/ -- P30 DK043351/DK/NIDDK NIH HHS/ -- R01 CA085681/CA/NCI NIH HHS/ -- R01 CA085681-06/CA/NCI NIH HHS/ -- R01 CA142805/CA/NCI NIH HHS/ -- R01 CA142805-01/CA/NCI NIH HHS/ -- RL1CA133834/CA/NCI NIH HHS/ -- RL1GM084437/GM/NIGMS NIH HHS/ -- RL1HG004671/HG/NHGRI NIH HHS/ -- UL1RR024924/RR/NCRR NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2011 Jul 13;475(7355):231-4. doi: 10.1038/nature10167.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Building 149 13th Street, Charlestown, Massachusetts 02129, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21753854" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Apoptosis/*drug effects ; Breast Neoplasms/*drug therapy/genetics/metabolism/*pathology ; Cell Line ; Cell Line, Tumor ; Cell Transformation, Neoplastic ; Comet Assay ; DNA Damage/drug effects ; Dioxolanes/adverse effects/chemistry/*pharmacology ; Genotype ; Mice ; Neoplasm Metastasis/drug therapy/pathology ; Oxidative Stress/*drug effects ; Reactive Oxygen Species/*metabolism ; Small Molecule Libraries/chemistry ; Xenograft Model Antitumor Assays
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2012-07-17
    Description: Recombination between herpesviruses has been seen in vitro and in vivo under experimental conditions. This has raised safety concerns about using attenuated herpesvirus vaccines in human and veterinary medicine and adds to other known concerns associated with their use, including reversion to virulence and disease arising from recurrent reactivation of lifelong chronic infection. We used high-throughput sequencing to investigate relationships between emergent field strains and vaccine strains of infectious laryngotracheitis virus (ILTV, gallid herpesvirus 1). We show that independent recombination events between distinct attenuated vaccine strains resulted in virulent recombinant viruses that became the dominant strains responsible for widespread disease in Australian commercial poultry flocks. These findings highlight the risks of using multiple different attenuated herpesvirus vaccines, or vectors, in the same populations.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, Sang-Won -- Markham, Philip F -- Coppo, Mauricio J C -- Legione, Alistair R -- Markham, John F -- Noormohammadi, Amir H -- Browning, Glenn F -- Ficorilli, Nino -- Hartley, Carol A -- Devlin, Joanne M -- New York, N.Y. -- Science. 2012 Jul 13;337(6091):188. doi: 10.1126/science.1217134.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Asia-Pacific Centre for Animal Health, Faculty of Veterinary Science, The University of Melbourne, Parkville, Victoria 3010, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22798607" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Chickens ; DNA, Viral/genetics ; Genome, Viral ; Herpesviridae Infections/*veterinary/virology ; Herpesvirus 1, Gallid/*genetics/immunology/*pathogenicity/physiology ; *Herpesvirus Vaccines ; High-Throughput Nucleotide Sequencing ; Molecular Sequence Data ; Polymorphism, Single Nucleotide ; Poultry Diseases/*virology ; *Recombination, Genetic ; Sequence Analysis, DNA ; Specific Pathogen-Free Organisms ; Vaccines, Attenuated ; Virulence ; Virus Replication
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2013-10-12
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, Sang-Won -- Han, Sang-Wook -- Sririyanum, Malinee -- Park, Chang-Jin -- Seo, Young-Su -- Ronald, Pamela C -- New York, N.Y. -- Science. 2013 Oct 11;342(6155):191. doi: 10.1126/science.342.6155.191-a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Plant Molecular Systems Biotech, Kyung Hee University, Yongin, Korea.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24115421" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2011-10-21
    Description: In nature, helical macromolecules such as collagen, chitin and cellulose are critical to the morphogenesis and functionality of various hierarchically structured materials. During tissue formation, these chiral macromolecules are secreted and undergo self-templating assembly, a process whereby multiple kinetic factors influence the assembly of the incoming building blocks to produce non-equilibrium structures. A single macromolecule can form diverse functional structures when self-templated under different conditions. Collagen type I, for instance, forms transparent corneal tissues from orthogonally aligned nematic fibres, distinctively coloured skin tissues from cholesteric phase fibre bundles, and mineralized tissues from hierarchically organized fibres. Nature's self-templated materials surpass the functional and structural complexity achievable by current top-down and bottom-up fabrication methods. However, self-templating has not been thoroughly explored for engineering synthetic materials. Here we demonstrate the biomimetic, self-templating assembly of chiral colloidal particles (M13 phage) into functional materials. A single-step process produces long-range-ordered, supramolecular films showing multiple levels of hierarchical organization and helical twist. Three distinct supramolecular structures are created by this approach: nematic orthogonal twists, cholesteric helical ribbons and smectic helicolidal nanofilaments. Both chiral liquid crystalline phase transitions and competing interfacial forces at the interface are found to be critical factors in determining the morphology of the templated structures during assembly. The resulting materials show distinctive optical and photonic properties, functioning as chiral reflector/filters and structural colour matrices. In addition, M13 phages with genetically incorporated bioactive peptide ligands direct both soft and hard tissue growth in a hierarchically organized manner. Our assembly approach provides insight into the complexities of hierarchical assembly in nature and could be expanded to other chiral molecules to engineer sophisticated functional helical-twisted structures.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chung, Woo-Jae -- Oh, Jin-Woo -- Kwak, Kyungwon -- Lee, Byung Yang -- Meyer, Joel -- Wang, Eddie -- Hexemer, Alexander -- Lee, Seung-Wuk -- R21DE018360/DE/NIDCR NIH HHS/ -- England -- Nature. 2011 Oct 19;478(7369):364-8. doi: 10.1038/nature10513.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Bioengineering, University of California, Berkeley, California 94720, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22012394" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bacteriophage M13/chemistry/*physiology ; Biomimetic Materials/chemical synthesis/*chemistry ; Cell Line ; Macromolecular Substances/chemistry ; Mice ; Optical Rotation ; Tissue Culture Techniques/instrumentation ; Virion/chemistry
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 5
    Publication Date: 2015-09-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Raj, Lakshmi -- Ide, Takao -- Gurkar, Aditi U -- Foley, Michael -- Schenone, Monica -- Li, Xiaoyu -- Tolliday, Nicola J -- Golub, Todd R -- Carr, Steven A -- Shamji, Alykhan F -- Stern, Andrew M -- Mandinova, Anna -- Schreiber, Stuart L -- Lee, Sam W -- England -- Nature. 2015 Oct 22;526(7574):596. doi: 10.1038/nature15370. Epub 2015 Sep 16.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26375002" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 6
    Publication Date: 2015-10-03
    Description: Memory stabilization after learning requires translational and transcriptional regulations in the brain, yet the temporal molecular changes that occur after learning have not been explored at the genomic scale. We used ribosome profiling and RNA sequencing to quantify the translational status and transcript levels in the mouse hippocampus after contextual fear conditioning. We revealed three types of repressive regulations: translational suppression of ribosomal protein-coding genes in the hippocampus, learning-induced early translational repression of specific genes, and late persistent suppression of a subset of genes via inhibition of estrogen receptor 1 (ESR1/ERalpha) signaling. In behavioral analyses, overexpressing Nrsn1, one of the newly identified genes undergoing rapid translational repression, or activating ESR1 in the hippocampus impaired memory formation. Collectively, this study unveils the yet-unappreciated importance of gene repression mechanisms for memory formation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cho, Jun -- Yu, Nam-Kyung -- Choi, Jun-Hyeok -- Sim, Su-Eon -- Kang, SukJae Joshua -- Kwak, Chuljung -- Lee, Seung-Woo -- Kim, Ji-il -- Choi, Dong Il -- Kim, V Narry -- Kaang, Bong-Kiun -- New York, N.Y. -- Science. 2015 Oct 2;350(6256):82-7. doi: 10.1126/science.aac7368.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for RNA Research, Institute for Basic Science, Seoul 151-742, Korea. Department of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul 151-747, Korea. ; Department of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul 151-747, Korea. ; Center for RNA Research, Institute for Basic Science, Seoul 151-742, Korea. Department of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul 151-747, Korea. narrykim@snu.ac.kr kaang@snu.ac.kr. ; Department of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul 151-747, Korea. narrykim@snu.ac.kr kaang@snu.ac.kr.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26430118" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Conditioning, Classical ; Estrogen Receptor alpha/*genetics ; Fear ; *Gene Expression Regulation ; Hippocampus/*metabolism ; Male ; Membrane Proteins/*genetics ; *Memory ; Mice ; Mice, Inbred C57BL ; Protein Biosynthesis/*genetics ; Ribosomal Proteins/genetics ; Transcription, Genetic
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 7
    Publication Date: 2015-08-01
    Description: The inefficient clearance of dying cells can lead to abnormal immune responses, such as unresolved inflammation and autoimmune conditions. We show that tumor suppressor p53 controls signaling-mediated phagocytosis of apoptotic cells through its target, Death Domain1alpha (DD1alpha), which suggests that p53 promotes both the proapoptotic pathway and postapoptotic events. DD1alpha appears to function as an engulfment ligand or receptor that engages in homophilic intermolecular interaction at intercellular junctions of apoptotic cells and macrophages, unlike other typical scavenger receptors that recognize phosphatidylserine on the surface of dead cells. DD1alpha-deficient mice showed in vivo defects in clearing dying cells, which led to multiple organ damage indicative of immune dysfunction. p53-induced expression of DD1alpha thus prevents persistence of cell corpses and ensures efficient generation of precise immune responses.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yoon, Kyoung Wan -- Byun, Sanguine -- Kwon, Eunjeong -- Hwang, So-Young -- Chu, Kiki -- Hiraki, Masatsugu -- Jo, Seung-Hee -- Weins, Astrid -- Hakroush, Samy -- Cebulla, Angelika -- Sykes, David B -- Greka, Anna -- Mundel, Peter -- Fisher, David E -- Mandinova, Anna -- Lee, Sam W -- CA142805/CA/NCI NIH HHS/ -- CA149477/CA/NCI NIH HHS/ -- CA80058/CA/NCI NIH HHS/ -- DK062472/DK/NIDDK NIH HHS/ -- DK091218/DK/NIDDK NIH HHS/ -- DK093378/DK/NIDDK NIH HHS/ -- DK57683/DK/NIDDK NIH HHS/ -- S10RR027673/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 2015 Jul 31;349(6247):1261669. doi: 10.1126/science.1261669.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Building 149, 13th Street, Charlestown, MA 02129, USA. ; Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA 02115, USA. ; Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA. ; Center for Regenerative Medicine and Technology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. ; Department of Medicine, Glom-NExT Center for Glomerular Kidney Disease and Novel Experimental Therapeutics, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA 02115, USA. ; Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Building 149, 13th Street, Charlestown, MA 02129, USA. Broad Institute of Harvard and MIT, 7 Cambridge Center, Cambridge, MA 02142, USA. ; Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Building 149, 13th Street, Charlestown, MA 02129, USA. Broad Institute of Harvard and MIT, 7 Cambridge Center, Cambridge, MA 02142, USA. swlee@mgh.harvard.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26228159" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Apoptosis/genetics/*immunology ; Autoimmune Diseases/genetics/immunology ; Cell Line, Tumor ; Female ; Humans ; Inflammation/genetics/immunology ; Macrophages/immunology ; Male ; Membrane Proteins/genetics/*metabolism ; Mice ; Mice, Knockout ; Molecular Sequence Data ; Phagocytosis/*immunology ; Phosphatidylserines/*metabolism ; Signal Transduction ; Tumor Suppressor Protein p53/*metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 8
    ISSN: 0922-338X
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Process Engineering, Biotechnology, Nutrition Technology
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Gene 105 (1991), S. 249-253 
    ISSN: 0378-1119
    Keywords: Lycopersicon esculentum ; Nicotiana rustica ; recombinant DNA ; tandem repeats ; tobacco ; tomato
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 0922-338X
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Process Engineering, Biotechnology, Nutrition Technology
    Type of Medium: Electronic Resource
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