@phdthesis{Koster2006, author = {Koster, Joachim}, title = {Polarisations-sensitive Resonanz-CARS- und Resonanz-Raman-Spektroskopie an metallfreien Porphyrinen}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-20358}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2006}, abstract = {Es werden in dieser Arbeit Raman-spektroskopische Untersuchungen an metallfreien Porphyrinen in verd{\"u}nnter L{\"o}sung vorgestellt. Dabei werden Laseranregungswellenl{\"a}ngen eingesetzt, die mit elektronischen Resonanzen der Porphyrine zusammenfallen. Die Ausnutzung von Resonanz-Effekten hat zum einen den Vorteil, dass gewisse Raman-Banden, je nach der Symmetrie der zugrunde liegenden Molek{\"u}lschwingung, eine deutliche Intensit{\"a}tsverst{\"a}rkung erfahren k{\"o}nnen, was den Nachweis auch geringer Probenkonzentrationen erm{\"o}glicht. Zum anderen sind anhand der Banden-Parameter R{\"u}ckschl{\"u}sse auf die exakte Molek{\"u}lsymmetrie m{\"o}glich. Im Vergleich zu Metalloporphyrinen sind f{\"u}r metallfreie Porphyrine bisher nur wenige Daten aus resonanten Raman-Spektren bekannt. Ein Grund hierf{\"u}r ist, dass letztere ein h{\"o}heres Maß an Fluoreszenz zeigen, die die Raman-Signale {\"u}berlagert. W{\"a}hrend bei Laseranregungen im Bereich hochenergetischer elektronischer Absorptionen der Porphyrine (B-Banden-Region) die klassische spontane Raman-Spektroskopie noch angewendet werden kann, ist dies im Bereich niederenergetischer Absorptionen (Q-Banden-Region) meist nicht mehr m{\"o}glich. Um auch Anregungen in der Q-Banden-Region zu verwirklichen, wird daher in dieser Arbeit von der koh{\"a}renten anti-Stokesschen Raman-Streuung (coherent anti-Stokes Raman scattering, CARS) Gebrauch gemacht. Die CARS-Spektroskopie erm{\"o}glicht es, das Fluoreszenzproblem zu umgehen, und bietet zudem noch weitere Vorteile, z. B. bez{\"u}glich der Unterscheidbarkeit spektral benachbarter Banden sowie bez{\"u}glich der Bestimmung symmetrierelevanter Parameter. Raman-Banden-Parameter aus Q-Banden-CARS-Spektren konnten hier f{\"u}r vier metallfreie Porphyrine, die sich im Substitutionsmuster an den beta-Kohlenstoffatomen des Tetrapyrrol-Makrozyklus unterscheiden, erhalten werden. Die CARS-Parameter, in Kombination mit Parametern aus spontanen B-Banden-Raman-Spektren sowie mit quantenchemisch berechneten Schwingungsvektoren, ließen den Schluss zu, dass Symmetrieunterschiede zwischen den Makrozyklen dieser Molek{\"u}le zwar gering, aber durchaus feststellbar sind. Desweiteren konnten durch die niederenergetische Anregung f{\"u}r die metallfreien Porphyrine spezifische Resonanzeffekte nachgewiesen werden, die z. T. von den f{\"u}r Metalloporphyrine bekannten Mustern abweichen.}, subject = {Porphyrine}, language = {de} } @article{KosterGurumurthyKumaretal.2022, author = {Koster, Stefanie and Gurumurthy, Rajendra Kumar and Kumar, Naveen and Prakash, Pon Ganish and Dhanraj, Jayabhuvaneshwari and Bayer, Sofia and Berger, Hilmar and Kurian, Shilpa Mary and Drabkina, Marina and Mollenkopf, Hans-Joachim and Goosmann, Christian and Brinkmann, Volker and Nagel, Zachary and Mangler, Mandy and Meyer, Thomas F. and Chumduri, Cindrilla}, title = {Modelling Chlamydia and HPV co-infection in patient-derived ectocervix organoids reveals distinct cellular reprogramming}, series = {Nature Communications}, volume = {13}, journal = {Nature Communications}, number = {1}, doi = {10.1038/s41467-022-28569-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-301349}, year = {2022}, abstract = {Coinfections with pathogenic microbes continually confront cervical mucosa, yet their implications in pathogenesis remain unclear. Lack of in-vitro models recapitulating cervical epithelium has been a bottleneck to study coinfections. Using patient-derived ectocervical organoids, we systematically modeled individual and coinfection dynamics of Human papillomavirus (HPV)16 E6E7 and Chlamydia, associated with carcinogenesis. The ectocervical stem cells were genetically manipulated to introduce E6E7 oncogenes to mimic HPV16 integration. Organoids from these stem cells develop the characteristics of precancerous lesions while retaining the self-renewal capacity and organize into mature stratified epithelium similar to healthy organoids. HPV16 E6E7 interferes with Chlamydia development and induces persistence. Unique transcriptional and post-translational responses induced by Chlamydia and HPV lead to distinct reprogramming of host cell processes. Strikingly, Chlamydia impedes HPV-induced mechanisms that maintain cellular and genome integrity, including mismatch repair in the stem cells. Together, our study employing organoids demonstrates the hazard of multiple infections and the unique cellular microenvironment they create, potentially contributing to neoplastic progression.}, language = {en} } @article{GroebnerWorstWeischenfeldtetal.2018, author = {Gr{\"o}bner, Susanne N. and Worst, Barbara C. and Weischenfeldt, Joachim and Buchhalter, Ivo and Kleinheinz, Kortine and Rudneva, Vasilisa A. and Johann, Pascal D. and Balasubramanian, Gnana Prakash and Segura-Wang, Maia and Brabetz, Sebastian and Bender, Sebastian and Hutter, Barbara and Sturm, Dominik and Pfaff, Elke and H{\"u}bschmann, Daniel and Zipprich, Gideon and Heinold, Michael and Eils, J{\"u}rgen and Lawerenz, Christian and Erkek, Serap and Lambo, Sander and Waszak, Sebastian and Blattmann, Claudia and Borkhardt, Arndt and Kuhlen, Michaela and Eggert, Angelika and Fulda, Simone and Gessler, Manfred and Wegert, Jenny and Kappler, Roland and Baumhoer, Daniel and Stefan, Burdach and Kirschner-Schwabe, Renate and Kontny, Udo and Kulozik, Andreas E. and Lohmann, Dietmar and Hettmer, Simone and Eckert, Cornelia and Bielack, Stefan and Nathrath, Michaela and Niemeyer, Charlotte and Richter, G{\"u}nther H. and Schulte, Johannes and Siebert, Reiner and Westermann, Frank and Molenaar, Jan J. and Vassal, Gilles and Witt, Hendrik and Burkhardt, Birgit and Kratz, Christian P. and Witt, Olaf and van Tilburg, Cornelis M. and Kramm, Christof M. and Fleischhack, Gudrun and Dirksen, Uta and Rutkowski, Stefan and Fr{\"u}hwald, Michael and Hoff, Katja von and Wolf, Stephan and Klingebeil, Thomas and Koscielniak, Ewa and Landgraf, Pablo and Koster, Jan and Resnick, Adam C. and Zhang, Jinghui and Liu, Yanling and Zhou, Xin and Waanders, Angela J. and Zwijnenburg, Danny A. and Raman, Pichai and Brors, Benedikt and Weber, Ursula D. and Northcott, Paul A. and Pajtler, Kristian W. and Kool, Marcel and Piro, Rosario M. and Korbel, Jan O. and Schlesner, Matthias and Eils, Roland and Jones, David T. W. and Lichter, Peter and Chavez, Lukas and Zapatka, Marc and Pfister, Stefan M.}, title = {The landscape of genomic alterations across childhood cancers}, series = {Nature}, volume = {555}, journal = {Nature}, organization = {ICGC PedBrain-Seq Project, ICGC MMML-Seq Project,}, doi = {10.1038/nature25480}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-229579}, pages = {321-327}, year = {2018}, abstract = {Pan-cancer analyses that examine commonalities and differences among various cancer types have emerged as a powerful way to obtain novel insights into cancer biology. Here we present a comprehensive analysis of genetic alterations in a pan-cancer cohort including 961 tumours from children, adolescents, and young adults, comprising 24 distinct molecular types of cancer. Using a standardized workflow, we identified marked differences in terms of mutation frequency and significantly mutated genes in comparison to previously analysed adult cancers. Genetic alterations in 149 putative cancer driver genes separate the tumours into two classes: small mutation and structural/copy-number variant (correlating with germline variants). Structural variants, hyperdiploidy, and chromothripsis are linked to TP53 mutation status and mutational signatures. Our data suggest that 7-8\% of the children in this cohort carry an unambiguous predisposing germline variant and that nearly 50\% of paediatric neoplasms harbour a potentially druggable event, which is highly relevant for the design of future clinical trials.}, language = {en} }