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  • 1
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    Corrigendum: Fatty acid carbon is essential for dNTP synthesis in endothelial cells (2015)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2015-08-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schoors, Sandra -- Bruning, Ulrike -- Missiaen, Rindert -- Queiroz, Karla C S -- Borgers, Gitte -- Elia, Ilaria -- Zecchin, Annalisa -- Cantelmo, Anna Rita -- Christen, Stefan -- Goveia, Jermaine -- Heggermont, Ward -- Godde, Lucica -- Vinckier, Stefan -- Van Veldhoven, Paul P -- Eelen, Guy -- Schoonjans, Luc -- Gerhardt, Holger -- Dewerchin, Mieke -- Baes, Myriam -- De Bock, Katrien -- Ghesquiere, Bart -- Lunt, Sophia Y -- Fendt, Sarah-Maria -- Carmeliet, Peter -- England -- Nature. 2015 Oct 1;526(7571):144. doi: 10.1038/nature14624. Epub 2015 Aug 5.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26245368" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 2
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    Fatty acid carbon is essential for dNTP synthesis in endothelial cells (2015)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2015-04-02
    Description: The metabolism of endothelial cells during vessel sprouting remains poorly studied. Here we report that endothelial loss of CPT1A, a rate-limiting enzyme of fatty acid oxidation (FAO), causes vascular sprouting defects due to impaired proliferation, not migration, of human and murine endothelial cells. Reduction of FAO in endothelial cells did not cause energy depletion or disturb redox homeostasis, but impaired de novo nucleotide synthesis for DNA replication. Isotope labelling studies in control endothelial cells showed that fatty acid carbons substantially replenished the Krebs cycle, and were incorporated into aspartate (a nucleotide precursor), uridine monophosphate (a precursor of pyrimidine nucleoside triphosphates) and DNA. CPT1A silencing reduced these processes and depleted endothelial cell stores of aspartate and deoxyribonucleoside triphosphates. Acetate (metabolized to acetyl-CoA, thereby substituting for the depleted FAO-derived acetyl-CoA) or a nucleoside mix rescued the phenotype of CPT1A-silenced endothelial cells. Finally, CPT1 blockade inhibited pathological ocular angiogenesis in mice, suggesting a novel strategy for blocking angiogenesis.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4413024/" 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/PMC4413024/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schoors, Sandra -- Bruning, Ulrike -- Missiaen, Rindert -- Queiroz, Karla C S -- Borgers, Gitte -- Elia, Ilaria -- Zecchin, Annalisa -- Cantelmo, Anna Rita -- Christen, Stefan -- Goveia, Jermaine -- Heggermont, Ward -- Godde, Lucica -- Vinckier, Stefan -- Van Veldhoven, Paul P -- Eelen, Guy -- Schoonjans, Luc -- Gerhardt, Holger -- Dewerchin, Mieke -- Baes, Myriam -- De Bock, Katrien -- Ghesquiere, Bart -- Lunt, Sophia Y -- Fendt, Sarah-Maria -- Carmeliet, Peter -- 269073/European Research Council/International -- England -- Nature. 2015 Apr 9;520(7546):192-7. doi: 10.1038/nature14362. Epub 2015 Apr 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Laboratory of Angiogenesis and Neurovascular link, Department of Oncology, KU Leuven, B-3000 Leuven, Belgium [2] Laboratory of Angiogenesis and Neurovascular Link, Vesalius Research Center, VIB, B-3000 Leuven, Belgium. ; 1] Laboratory of Cellular Metabolism and Metabolic Regulation, Department of Oncology, KU Leuven, B-3000 Leuven, Belgium [2] Laboratory of Cellular Metabolism and Metabolic Regulation, Vesalius Research Center, VIB, B-3000 Leuven, Belgium. ; Center for Molecular &Vascular Biology, Department of Cardiovascular Research, KU Leuven; Division of Clinical Cardiology, UZ Leuven, B-3000 Leuven, Belgium. ; Laboratory of Lipid Biochemistry and Protein Interactions, KU Leuven, B-3000 Leuven, Belgium. ; 1] Vascular Patterning Laboratory, Department of Oncology, KU Leuven, B-3000 Leuven, Belgium [2] Vascular Patterning Laboratory, Vesalius Research Center, VIB, B-3000 Leuven, Belgium [3] Integrative Vascular Biology Laboratory, Max Delbruck Center for Molecular Medicine, 13125 Berlin, Germany. ; Laboratory of Cell Metabolism, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, B-3000 Leuven, Belgium. ; 1] Laboratory of Angiogenesis and Neurovascular link, Department of Oncology, KU Leuven, B-3000 Leuven, Belgium [2] Laboratory of Angiogenesis and Neurovascular Link, Vesalius Research Center, VIB, B-3000 Leuven, Belgium [3] Exercise Physiology Research Group, Department of Kinesiology, KU Leuven, B-3001 Leuven, Belgium. ; Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan 48824, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25830893" target="_blank"〉PubMed〈/a〉
    Keywords: Acetic Acid/pharmacology ; Adenosine Triphosphate/metabolism ; Animals ; Blood Vessels/cytology/drug effects/metabolism/pathology ; Carbon/*metabolism ; Carnitine O-Palmitoyltransferase/antagonists & ; inhibitors/deficiency/genetics/metabolism ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Citric Acid Cycle ; DNA/biosynthesis ; Disease Models, Animal ; Endothelial Cells/cytology/drug effects/enzymology/*metabolism ; Fatty Acids/*chemistry/*metabolism ; Gene Silencing ; Glucose/metabolism ; Human Umbilical Vein Endothelial Cells/cytology/drug effects/metabolism/pathology ; Humans ; Mice ; Neovascularization, Pathologic/drug therapy/metabolism/pathology ; Nucleotides/*biosynthesis/chemistry/pharmacology ; Oxidation-Reduction/drug effects ; Retinopathy of Prematurity/drug therapy/metabolism/pathology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 3
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    Improved understanding of the searching behavior of ant colony optimization algorithms applied to the water distribution design problem (2012)
    Wiley
    Details
    Publication Date: 2012-09-05
    Description: Evolutionary algorithms (EAs) have been applied successfully to many water resource problems, such as system design, management decision formulation, and model calibration. The performance of an EA with respect to a particular problem type is dependent on how effectively its internal operators balance the exploitation/exploration trade-off to iteratively find solutions of an increasing quality. For a given problem, different algorithms are observed to produce a variety of different final performances, but there have been surprisingly few investigations into characterizing how the different internal mechanisms alter the algorithm's searching behavior, in both the objective and decision space, to arrive at this final performance. This paper presents metrics for analyzing the searching behavior of ant colony optimization algorithms, a particular type of EA, for the optimal water distribution system design problem, which is a classical NP-hard problem in civil engineering. Using the proposed metrics, behavior is characterized in terms of three different attributes: (1) the effectiveness of the search in improving its solution quality and entering into optimal or near-optimal regions of the search space, (2) the extent to which the algorithm explores as it converges to solutions, and (3) the searching behavior with respect to the feasible and infeasible regions. A range of case studies is considered, where a number of ant colony optimization variants are applied to a selection of water distribution system optimization problems. The results demonstrate the utility of the proposed metrics to give greater insight into how the internal operators affect each algorithm's searching behavior.
    Print ISSN: 0043-1397
    Electronic ISSN: 1944-7973
    Topics: Architecture, Civil Engineering, Surveying , Geography
    Published by Wiley on behalf of American Geophysical Union (AGU).
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  • 4
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    Improved understanding of the searching behavior of ant colony optimization algorithms applied to the water distribution design problem (2013)
    Wiley
    Details
    Publication Date: 2013-01-03
    Description: [1]  Evolutionary algorithms (EAs) have been applied successfully to many water resource problems, such as system design, management decision formulation, and model calibration. The performance of an EA with respect to a particular problem type is dependent on how effectively its internal operators balance the exploitation/exploration trade-off to iteratively find solutions of an increasing quality. For a given problem, different algorithms are observed to produce a variety of different final performances, but there have been surprisingly few investigations into characterizing how the different internal mechanisms alter the algorithm's searching behavior, in both the objective and decision space, to arrive at this final performance. This paper presents metrics for analyzing the searching behavior of ant colony optimization algorithms, a particular type of EA, for the optimal water distribution system design problem, which is a classical NP-hard problem in civil engineering. Using the proposed metrics, behavior is characterized in terms of three different attributes: (1) the effectiveness of the search in improving its solution quality and entering into optimal or near-optimal regions of the search space, (2) the extent to which the algorithm explores as it converges to solutions, and (3) the searching behavior with respect to the feasible and infeasible regions. A range of case studies is considered, where a number of ant colony optimization variants are applied to a selection of water distribution system optimization problems. The results demonstrate the utility of the proposed metrics to give greater insight into how the internal operators affect each algorithm's searching behavior.
    Print ISSN: 0043-1397
    Electronic ISSN: 1944-7973
    Topics: Architecture, Civil Engineering, Surveying , Geography
    Published by Wiley on behalf of American Geophysical Union (AGU).
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