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  • 1
    Publication Date: 2014-11-27
    Description: Spinocerebellar ataxia type 17 (SCA17) is an autosomal dominant cerebellar ataxia caused by the expansion of polyglutamine (polyQ) within the TATA box-binding protein (TBP). Previous studies have shown that polyQ-expanded TBP forms neurotoxic aggregates and alters downstream genes. However, how expanded polyQ tracts affect the function of TBP and the link between dysfunctional TBP and SCA17 is not clearly understood. In this study, we generated novel Drosophila models for SCA17 that recapitulate pathological features such as aggregate formation, mobility defects and premature death. In addition to forming neurotoxic aggregates, we determined that polyQ-expanded TBP reduces its own intrinsic DNA-binding and transcription abilities. Dysfunctional TBP also disrupts normal TBP function. Furthermore, heterozygous dTbp amorph mutant flies exhibited SCA17-like phenotypes and flies expressing polyQ-expanded TBP exhibited enhanced retinal degeneration, suggesting that loss of TBP function may contribute to SCA17 pathogenesis. We further determined that the downregulation of TBP activity enhances retinal degeneration in SCA3 and Huntington's disease fly models, indicating that the deactivation of TBP is likely to play a common role in polyQ-induced neurodegeneration.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
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  • 2
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2012-10-09
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schwabe, Robert F -- Wang, Timothy C -- New York, N.Y. -- Science. 2012 Oct 5;338(6103):52-3. doi: 10.1126/science.1229905.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, Columbia University, New York, NY 10032, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23042875" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Carcinoma/*microbiology ; Colitis/*complications ; Colorectal Neoplasms/*microbiology ; *DNA Damage ; Intestines/*microbiology ; Metagenome/*physiology
    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: 2004-11-30
    Description: Epithelial cancers are believed to originate from transformation of tissue stem cells. However, bone marrow-derived cells (BMDCs), which are frequently recruited to sites of tissue injury and inflammation, might also represent a potential source of malignancy. We show that although acute injury, acute inflammation, or transient parietal cell loss within the stomach do not lead to BMDC recruitment, chronic infection of C57BL/6 mice with Helicobacter, a known carcinogen, induces repopulation of the stomach with BMDCs. Subsequently, these cells progress through metaplasia and dysplasia to intraepithelial cancer. These findings suggest that epithelial cancers can originate from marrow-derived sources and thus have broad implications for the multistep model of cancer progression.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Houghton, Jeanmarie -- Stoicov, Calin -- Nomura, Sachiyo -- Rogers, Arlin B -- Carlson, Jane -- Li, Hanchen -- Cai, Xun -- Fox, James G -- Goldenring, James R -- Wang, Timothy C -- CA95103/CA/NCI NIH HHS/ -- K22 CA90518/CA/NCI NIH HHS/ -- R01 CA87958/CA/NCI NIH HHS/ -- R01 DK58/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 2004 Nov 26;306(5701):1568-71.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine and Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA. jeanmarie.houghton@umassmed.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15567866" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Apoptosis ; Bone Marrow Cells/*cytology ; Bone Marrow Transplantation ; Carcinoma in Situ/pathology ; Cell Differentiation ; Cell Fusion ; Disease Progression ; Female ; Gastric Mucosa/chemistry/pathology ; Gastritis/*pathology ; Helicobacter Infections/*pathology ; *Helicobacter felis ; Keratins/analysis ; Male ; Mesenchymal Stromal Cells/physiology ; Metaplasia ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Mucins/analysis ; Muscle Proteins/analysis ; Parietal Cells, Gastric/physiology ; Peptides/analysis ; Phenotype ; Stem Cells/*physiology ; Stomach Neoplasms/*pathology
    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
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2009-01-31
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Neureiter, Norman P -- Wang, Tom C -- New York, N.Y. -- Science. 2009 Jan 30;323(5914):561. doi: 10.1126/science.1170938.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19179495" target="_blank"〉PubMed〈/a〉
    Keywords: China ; *International Cooperation ; *Science ; *Technology ; United States
    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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  • 5
    ISSN: 1520-5126
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0495
    Keywords: Pesticide migration ; Mosquito control impoundment ; Water management techniques
    Source: Springer Online Journal Archives 1860-2000
    Topics: Geosciences
    Notes: Abstract This project was designed to: (1) document the distribution and migration of organochlorine pesticide residues within marsh substrates of 18 St. Lucie County mosquito control impoundments located along the Indian River Lagoon estuary, and (2) evaluate the impact of water management techniques on residue mobility. Our results indicate that detectible concentrations of organochlorine compounds, applied between the late 1940s and early 1950s, are present in 16 of the 18 St. Lucie County mosquito control impoundments. These compounds are primarily restricted to the surficial, organic-rich wetland sediment, which, based upon geotechnical analysis, was exposed to the atmosphere at a time when the impoundments were subjected to pesticide treatment. Contaminated sediments are present below the surficial, organic-rich layer, suggesting that some vertical migration of pesticides has occurred. It is unlikely that leaching associated with the downward percolation of impounded water was responsible for this migration as pesticide residues were never detected within thein situ pore waters. An alternative explanation is that biological processes (e.g., rooting, burrowing) facilitated the downward flux of organochlorine compounds into sediment horizons not subjected to direct treatment. Eighty-eight surface water samples obtained from two impoundments subjected to contrasting water management techniques were analyzed for pesticide content. None of the surficial water samples collected in association with these impoundments contained detectible concentrations of organochlorine compounds. These samples were unfiltered and contained as much as 25 mg/1 of particulate organic matter. This suggests that the currently preferred management technique (RIM), which is designed to maintain water quality, limit mosquito production, and provide for ecological continuity, does not hydraulically mobilize pesticide residues into the Indian River Lagoon estuary.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Bulletin of environmental contamination and toxicology 60 (1998), S. 739-744 
    ISSN: 1432-0800
    Source: Springer Online Journal Archives 1860-2000
    Topics: Energy, Environment Protection, Nuclear Power Engineering , Medicine
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Acta mechanica solida Sinica 8 (1995), S. 95-109 
    ISSN: 0894-9166
    Keywords: simple polycrystal ; grain boundary
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Abstract A numerical investigation on the simple polycrystals containing three symmetrical tilt grain boundaries (GBs) is carried out within the framework of crystal plasticity which precisely considers the finite deformation and finite lattice rotation as well as elastic anisotropy. The calculated results show that the slip geometry and the redistribution of stresses arising from the anisotropy and boundary constraint play an important role in the plastic deformation in the simple polycrystals. The stress level along GB is sensitive to the load level and misorientation, and the stresses along GB are distributed nonuniformly. The GB may exhibit a softening or strengthening feature, which depends on the misorientation angle. The localized deformation bands usually develop accompanying the GB plastic deformation, the impingement of the localized band on the GB may result in another localized deformation band. The yield stresses with different misorientation angles are favorably compared with the experimental results.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 679 (1993), S. 0 
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Chemical Physics Letters 105 (1984), S. 233-236 
    ISSN: 0009-2614
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
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