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  • 1
    Keywords: p53 ; CANCER-CELLS ; COLON-CANCER ; MASS-SPECTROMETRY ; GEL-ELECTROPHORESIS ; HUMAN SMALL-INTESTINE ; LIPID-METABOLISM ; LIPOTOXICITY ; ACYL-COA SYNTHETASE-5 ; FATTY-ACID REGULATION
    Abstract: Acyl-CoA synthetase 5 (ACSL5), a mitochondrially localized enzyme, catalyzes the synthesis of long-chain fatty acid thioesters and is physiologically involved in pro-apoptotic sensing of enterocytes. The aim of the present study is to identify an ACSL5-dependent regulation of mitochondrially expressed proteins and the characterization of related pathways in normal and diseased human intestinal mucosa. Proteomics of isolated mitochondria from ACSL5 transfectants and CaCo2 controls were performed. ACSL5-dependent protein synthesis was verified with quantitative reverse transcription plus the polymerase chain reaction, Western blotting, short-interfering-RNA-mediated gene silencing and additional cell culture experiments. Lipid changes were analyzed with tandem mass spectrometry. ACSL5-related pathways were characterized in normal mucosa and sporadic adenocarcinomas of the human intestine. In CaCo2 cells transfected with ACSL5, mortalin (HSPA9) was about two-fold increased in mitochondria, whereas cytoplasmic mortalin levels were unchanged. Disturbance of acyl-CoA/sphingolipid metabolism, induced by ACSL5 over-expression, was characterized as crucial. ACSL5-related over-expression of mitochondrial mortalin was found in HEK293 and Lovo (wild-type TP53 [tumor protein p53]) and CaCo2 (p53-negative; TP53 mutated) cells but not in Colo320DM cells (mutated TP53). In normal human intestinal mucosa, an increasing gradient of both ACSL5 and mortalin from bottom to top was observed, whereas p53 (wild-type TP53) decreased. In sporadic intestinal adenocarcinomas with strong p53 immunostaining (mutated TP53), ACSL5-related mortalin expression was heterogeneous. ACSL5-induced mitochondrial mortalin expression is assumed to be a stress response to ACSL5-related changes in lipid metabolism and is regulated by the TP53 status. Uncoupling of ACSL5 and mitochondrial mortalin by mutated TP53 could be important in colorectal carcinogenesis.
    Type of Publication: Journal article published
    PubMed ID: 24770931
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  • 2
    ISSN: 1432-0703
    Source: Springer Online Journal Archives 1860-2000
    Topics: Energy, Environment Protection, Nuclear Power Engineering , Medicine
    Notes: Abstract The ontogenetic effects of the environmental carcinogen benzo(a)pyrene (BAP) on three species of larval flatfish were investigated using concentrations (from 0.10 to 4.2 ppb) which were comparable to levels found in polluted harbors. BAP-treated sand sole (Psettichthys melanostichus) eggs displayed a significant decline in hatching success and a significantly higher incidence of developmental anomalies than did control eggs. Flathead sole (Hippoglossoides elassodon) eggs exposed to a single dose of a water-soluble BAP-bovine serum albumin complex demonstrated evidence of toxie injury with pycnotic nuclei present in the integument and, more commonly, in ocular and neural tissues. An increased incidence of morphological anomalies in English sole (Parophyrs vetulus) eggs and larvae exposed to BAP was not detected.
    Type of Medium: Electronic Resource
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  • 3
    Publication Date: 2014-11-08
    Description: Supermassive black holes with masses of millions to billions of solar masses are commonly found in the centers of galaxies. Astronomers seek to image jet formation using radio interferometry but still suffer from insufficient angular resolution. An alternative method to resolve small structures is to measure the time variability of their emission. Here we report on gamma-ray observations of the radio galaxy IC 310 obtained with the MAGIC (Major Atmospheric Gamma-ray Imaging Cherenkov) telescopes, revealing variability with doubling time scales faster than 4.8 min. Causality constrains the size of the emission region to be smaller than 20% of the gravitational radius of its central black hole. We suggest that the emission is associated with pulsar-like particle acceleration by the electric field across a magnetospheric gap at the base of the radio jet.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Aleksic, J -- Ansoldi, S -- Antonelli, L A -- Antoranz, P -- Babic, A -- Bangale, P -- Barrio, J A -- Becerra Gonzalez, J -- Bednarek, W -- Bernardini, E -- Biasuzzi, B -- Biland, A -- Blanch, O -- Bonnefoy, S -- Bonnoli, G -- Borracci, F -- Bretz, T -- Carmona, E -- Carosi, A -- Colin, P -- Colombo, E -- Contreras, J L -- Cortina, J -- Covino, S -- Da Vela, P -- Dazzi, F -- De Angelis, A -- De Caneva, G -- De Lotto, B -- de Ona Wilhelmi, E -- Delgado Mendez, C -- Dominis Prester, D -- Dorner, D -- Doro, M -- Einecke, S -- Eisenacher, D -- Elsaesser, D -- Fonseca, M V -- Font, L -- Frantzen, K -- Fruck, C -- Galindo, D -- Garcia Lopez, R J -- Garczarczyk, M -- Garrido Terrats, D -- Gaug, M -- Godinovic, N -- Gonzalez Munoz, A -- Gozzini, S R -- Hadasch, D -- Hanabata, Y -- Hayashida, M -- Herrera, J -- Hildebrand, D -- Hose, J -- Hrupec, D -- Idec, W -- Kadenius, V -- Kellermann, H -- Kodani, K -- Konno, Y -- Krause, J -- Kubo, H -- Kushida, J -- La Barbera, A -- Lelas, D -- Lewandowska, N -- Lindfors, E -- Lombardi, S -- Longo, F -- Lopez, M -- Lopez-Coto, R -- Lopez-Oramas, A -- Lorenz, E -- Lozano, I -- Makariev, M -- Mallot, K -- Maneva, G -- Mankuzhiyil, N -- Mannheim, K -- Maraschi, L -- Marcote, B -- Mariotti, M -- Martinez, M -- Mazin, D -- Menzel, U -- Miranda, J M -- Mirzoyan, R -- Moralejo, A -- Munar-Adrover, P -- Nakajima, D -- Niedzwiecki, A -- Nilsson, K -- Nishijima, K -- Noda, K -- Orito, R -- Overkemping, A -- Paiano, S -- Palatiello, M -- Paneque, D -- Paoletti, R -- Paredes, J M -- Paredes-Fortuny, X -- Persic, M -- Poutanen, J -- Prada Moroni, P G -- Prandini, E -- Puljak, I -- Reinthal, R -- Rhode, W -- Ribo, M -- Rico, J -- Rodriguez Garcia, J -- Rugamer, S -- Saito, T -- Saito, K -- Satalecka, K -- Scalzotto, V -- Scapin, V -- Schultz, C -- Schweizer, T -- Shore, S N -- Sillanpaa, A -- Sitarek, J -- Snidaric, I -- Sobczynska, D -- Spanier, F -- Stamatescu, V -- Stamerra, A -- Steinbring, T -- Storz, J -- Strzys, M -- Takalo, L -- Takami, H -- Tavecchio, F -- Temnikov, P -- Terzic, T -- Tescaro, D -- Teshima, M -- Thaele, J -- Tibolla, O -- Torres, D F -- Toyama, T -- Treves, A -- Uellenbeck, M -- Vogler, P -- Zanin, R -- Kadler, M -- Schulz, R -- Ros, E -- Bach, U -- Krauss, F -- Wilms, J -- New York, N.Y. -- Science. 2014 Nov 28;346(6213):1080-4. doi: 10.1126/science.1256183. Epub 2014 Nov 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institut de Fisica d'Altes Energies, Campus UAB, E-08193 Bellaterra, Spain. ; Universita di Udine and Istituto Nazionale di Fisica Nucleare (INFN) Trieste, I-33100 Udine, Italy, and Istituto Nazionale di Astrofisica (INAF)-Trieste, I-34127 Trieste, Italy. ; INAF National Institute for Astrophysics, I-00136 Rome, Italy. ; Universita di Siena and INFN Pisa, I-53100 Siena, Italy. ; Croatian MAGIC Consortium, Rudjer Boskovic Institute, University of Rijeka and University of Split, HR-10000 Zagreb, Croatia. ; Max-Planck-Institut fur Physik, D-80805 Munchen, Germany. ; Universidad Complutense, E-28040 Madrid, Spain. ; Instituto de Astrofisica de Canarias, E-38200 La Laguna, Tenerife, Spain. Present address: NASA Goddard Space Flight Center, Greenbelt, MD 20771, USA, and Department of Physics and Department of Astronomy, University of Maryland, College Park, MD 20742, USA. ; University of Lodz', PL-90236 Lodz, Poland. ; Deutsches Elektronen-Synchrotron, D-15738 Zeuthen, Germany. ; ETH Zurich, CH-8093 Zurich, Switzerland. ; Universitat Wurzburg, D-97074 Wurzburg, Germany. Present address: Ecole Polytechnique Federale de Lausanne (EPFL), Lausanne, Switzerland. ; Centro de Investigaciones Energeticas, Medioambientales y Tecnologicas, E-28040 Madrid, Spain. ; Instituto de Astrofisica de Canarias, E-38200 La Laguna, Tenerife, Spain. ; Institute of Space Sciences, E-08193 Barcelona, Spain. ; Universitat Wurzburg, D-97074 Wurzburg, Germany. ; Universita di Padova and INFN, I-35131 Padova, Italy. ; Technische Universitat Dortmund, D-44221 Dortmund, Germany. ; Universitat Wurzburg, D-97074 Wurzburg, Germany. deisenacher@astro.uni-wuerzburg.de jsitarek@ifae.es mannheim@astro.uni-wuerzburg.de. ; Unitat de Fisica de les Radiacions, Departament de Fisica, and Centro de Estudios e Investigacion Espaciales-Institut d'Estudis Espacials de Catalunya, Universitat Autonoma de Barcelona, E-08193 Bellaterra, Spain. ; Universitat de Barcelona, Institut de Ciencies del Cosmos, Institut d'Estudis Espacials de Catalunya-Universitat de Barcelona, E-08028 Barcelona, Spain. ; Institute of Space Sciences, E-08193 Barcelona, Spain. Present address: Institut fur Astro- und Teilchenphysik, Leopold-Franzens-Universitat Innsbruck, A-6020 Innsbruck, Austria. ; Japanese MAGIC Consortium, Division of Physics and Astronomy, Kyoto University, Japan. ; Finnish MAGIC Consortium, Tuorla Observatory, University of Turku and Department of Physics, University of Oulu, Finland. ; Finnish MAGIC Consortium, Tuorla Observatory, University of Turku and Department of Physics, University of Oulu, Finland. Present address: Finnish Centre for Astronomy with ESO (FINCA), Turku, Finland. ; Deceased. ; Institute for Nuclear Research and Nuclear Energy, BG-1784 Sofia, Bulgaria. ; Universita di Udine and Istituto Nazionale di Fisica Nucleare (INFN) Trieste, I-33100 Udine, Italy, and Istituto Nazionale di Astrofisica (INAF)-Trieste, I-34127 Trieste, Italy. Present address: Astrophysics Science Division, Bhabha Atomic Research Centre, Mumbai 400085, India. ; Universita di Pisa and INFN Pisa, I-56126 Pisa, Italy. ; Institut de Fisica d'Altes Energies, Campus UAB, E-08193 Bellaterra, Spain. deisenacher@astro.uni-wuerzburg.de jsitarek@ifae.es mannheim@astro.uni-wuerzburg.de. ; Institut de Fisica d'Altes Energies, Campus UAB, E-08193 Bellaterra, Spain. Present address: School of Chemistry and Physics, University of Adelaide, Adelaide 5005, Australia. ; Max-Planck-Institut fur Physik, D-80805 Munchen, Germany. Japanese MAGIC Consortium, Division of Physics and Astronomy, Kyoto University, Japan. ; ICREA and Institute of Space Sciences, E-08193 Barcelona, Spain. ; Universita dell'Insubria and INFN Milano Bicocca, Como, I-22100 Como, Italy. ; Universitat Wurzburg, D-97074 Wurzburg, Germany. Dr. Remeis-Sternwarte Bamberg, Astronomisches Institut der Universitat Erlangen-Nurnberg, ECAP, D-96049 Bamberg, Germany. ; Max-Planck-Institut fur Radioastronomie, D-53121 Bonn, Germany. Observatori Astronomic, Universitat de Valencia, E-46980 Paterna, Valencia, Spain. Departament d'Astronomia i Astrofisica, Universitat de Valencia, E-46100 Burjassot, Valencia, Spain. ; Max-Planck-Institut fur Radioastronomie, D-53121 Bonn, Germany. ; Dr. Remeis-Sternwarte Bamberg, Astronomisches Institut der Universitat Erlangen-Nurnberg, ECAP, D-96049 Bamberg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25378461" 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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