Dokument-ID Dokumenttyp Autoren/innen Persönliche Herausgeber/innen Haupttitel Abstract Auflage Verlagsort Verlag Herausgeber (Institution) Erscheinungsjahr Titel des übergeordneten Werkes Jahrgang/Band ISBN Veranstaltung Veranstaltungsort Beginndatum der Veranstaltung Enddatum der Veranstaltung Ausgabe/Heft Erste Seite Letzte Seite URN DOI Lizenz Datum der Freischaltung OPUS4-32881 Zeitschriftenartikel Flohr, S.; Brinker, U.; Schramm, A.; Kierdorf, U.; Staude, Andreas; Piek, J.; Jantzen, D.; Hauenstein, K.; Orschiedt, J. Flint arrowhead embedded in a human humerus from the Bronze Age site in the Tollense valley, Germany - A high-resolution micro-CT study to distinguish antemortem from perimortem projectile trauma to bone The Bronze Age site in the Tollense valley, Germany, has yielded thousands of human and animal bones and a number of archaeological artifacts. Several of the human bones exhibit blunt and sharp force lesions, and the assemblage has been interpreted as representing victims of a large scale conflict. One of the earliest finds is a human humerus with an embedded flint arrowhead. Alleged signs of healing initially reported for this humerus based on clinical CT imaging were interpreted as evidence of an antemortem lesion. The present study, using micro-CT imaging, revealed that the arrowhead lesion in the humerus, contrary to the previous interpretation, shows no signs of healing. The structure previously assumed to represent a sclerotic margin around the wound canal was shown to actually represent compacted trabecular debris. Thus, our re-analysis of the specimen led to a re-classification of the arrow wound as a perimortem lesion. The findings of the present study demonstrate the value of micro-CT imaging as a non-destructive method for obtaining information on the nature of bone lesions and healing reactions critical for the reconstruction of interpersonal conflict scenarios in the past. Elsevier Inc. 2015 International journal of paleopathology 9 76 81 10.1016/j.ijpp.2015.02.004 2016-02-20 OPUS4-50719 Zeitschriftenartikel Tjaden, B.; Lisec, Jan; Schramm, A. N-Myc-induced metabolic rewiring creates novel therapeutic vulnerabilities in neuroblastoma N-Myc is a transcription factor that is aberrantly expressed in many tumor types and is often correlated with poor patient prognosis. Recently, several lines of evidence pointed to the fact that oncogenic activation of Myc family proteins is concomitant with reprogramming of tumor cells to cope with an enhanced need for metabolites during cell growth. These adaptions are driven by the ability of Myc proteins to act as transcriptional amplifiers in a tissue-of-origin specific manner. Here, we describe the effects of N-Myc overexpression on metabolic reprogramming in neuroblastoma cells. Ectopic expression of N-Myc induced a glycolytic switch that was concomitant with enhanced sensitivity towards 2-deoxyglucose, an inhibitor of glycolysis. Moreover, global metabolic profiling revealed extensive alterations in the cellular metabolome resulting from overexpression of N-Myc. Limited supply with either of the two main carbon sources, glucose or glutamine, resulted in distinct shifts in steady-state metabolite levels and significant changes in glutathione metabolism. Interestingly, interference with glutamine-glutamate conversion preferentially blocked proliferation of N-Myc overexpressing cells, when glutamine levels were reduced. Thus, our study uncovered N-Myc induction and nutrient levels as important metabolic master switches in neuroblastoma cells and identified critical nodes that restrict tumor cell proliferation. 2020 Scientific Reports 10 1 7157 urn:nbn:de:kobv:b43-507193 10.1038/s41598-020-64040-1 https://creativecommons.org/licenses/by/4.0/deed.de 2020-05-06 OPUS4-46815 Zeitschriftenartikel Tjaden, B.; Baum, K.; Marquardt, V.; Simon, M.; Trajkovic-Arsic, M.; Kouril, T.; Siebers, B.; Lisec, Jan; Siveke, J. T.; Schulte, J. H.; Benary, U.; Remke, M.; Wolf, J.; Schramm, A. MYCN-induced metabolic rewiring creates novel therapeutic vulnerabilities in neuroblastoma MYCN is a transcription factor that is aberrantly expressed in many tumor types and is often correlated with poor patient prognosis. Recently, several lines of evidence pointed to the fact that oncogenic activation of MYC family proteins is concomitant with reprogramming of tumor cells to cope with an enhanced need for metabolites during cell growth. These adaptions are driven by the ability of MYC proteins to act as transcriptional amplifiers in a tissue-of-origin specific manner. Here, we describe the effects of MYCN overexpression on metabolic reprogramming in neuroblastoma cells. Ectopic expression of MYCN induced a glycolytic switch that was concomitant with enhanced sensitivity towards 2-deoxyglucose, an inhibitor of glycolysis. Moreover, global metabolic profiling revealed extensive alterations in the cellular metabolome resulting from overexpression of MYCN. Limited supply with either of the two main carbon sources, glucose or glutamine, resulted in distinct shifts in steady-state metabolite levels and significant changes in glutathione metabolism. Interestingly, interference with glutamine-glutamate conversion preferentially blocked proliferation of MYCN overexpressing cells, when glutamine levels were reduced. Thus, our study uncovered MYCN induction and nutrient levels as important metabolic master switches in neuroblastoma cells and identified critical nodes that restrict tumor cell proliferation. Cold Spring Harbor, NY Cold Spring Harbor Laboratory 2018 bioRxiv : The preprint server for biology 1 21 10.1101/423756 2018-11-30