@phdthesis{Weh2024,
  author    = {Weh, Manuel},
  title     = {Chiral Perylene Bisimide Cyclophanes},
  doi       = {10.25972/OPUS-31529},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-315296},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {This work illustrates how the targeted tailoring of supramolecular cavities can not only accomplish high binding due to optimized stereoelectronic shape matches between host and guest but also how molecular engineering of the binding site by a refined substitution periphery of the cavity makes enantiospecific guest recognition and host mediated chirality transfer feasible. Moreover, an enzyme mimic, following the Pauling-Jencks model of enzyme catalysis was realized by the smart design of a PBI host composed of moderately twisted chromophores, which drives the substrate inversion according to the concepts of transition state stabilization and ground state destabilization. The results of this thesis contribute to a better understanding of structure-specific interactions in host-guest complexes as well as the corresponding thermodynamic and kinetic properties and represent an appealing blueprint for the design of new artificial complex structures of high stereoelectronic shape complementarity in order to achieve the goal of sophisticated supramolecular receptors and enzyme mimicry.},
  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}
}
@article{HarnošCanizalJuraseketal.2019,
  author    = {Harnoš, Jakub and Ca{\~n}izal, Maria Consuelo Alonso and Jur{\´a}sek, Miroslav and Kumar, Jitender and Holler, Cornelia and Schambony, Alexandra and Han{\´a}kov{\´a}, Kateřina and Bernat{\´i}k, Ondřej and Zdr{\´a}hal, Zbyn{\^e}k and G{\"o}m{\"o}ryov{\´a}, Krist{\´i}na and Gybeľ, Tom{\´a}š and Radaszkiewicz, Tomasz Witold and Kravec, Marek and Trant{\´i}rek, Luk{\´a}š and Ryneš, Jan and Dave, Zankruti and Fern{\´a}ndez-Llamazares, Ana Iris and V{\´a}cha, Robert and Tripsianes, Konstantinos and Hoffmann, Carsten and Bryja, V{\´i}tězslav},
  title     = {Dishevelled-3 conformation dynamics analyzed by FRET-based biosensors reveals a key role of casein kinase 1},
  series = {Nature Communications},
  volume    = {10},
  journal   = {Nature Communications},
  doi       = {10.1038/s41467-019-09651-7},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-227837},
  year      = {2019},
  abstract  = {Dishevelled (DVL) is the key component of the Wnt signaling pathway. Currently, DVL conformational dynamics under native conditions is unknown. To overcome this limitation, we develop the Fluorescein Arsenical Hairpin Binder- (FlAsH-) based FRET in vivo approach to study DVL conformation in living cells. Using this single-cell FRET approach, we demonstrate that (i) Wnt ligands induce open DVL conformation, (ii) DVL variants that are predominantly open, show more even subcellular localization and more efficient membrane recruitment by Frizzled (FZD) and (iii) Casein kinase 1 ɛ (CK1ɛ) has a key regulatory function in DVL conformational dynamics. In silico modeling and in vitro biophysical methods explain how CK1ɛ-specific phosphorylation events control DVL conformations via modulation of the PDZ domain and its interaction with DVL C-terminus. In summary, our study describes an experimental tool for DVL conformational sampling in living cells and elucidates the essential regulatory role of CK1ɛ in DVL conformational dynamics.},
  language  = {en}
}
@article{GottschalkRichterZiegleretal.2019,
  author    = {Gottschalk, Michael G. and Richter, Jan and Ziegler, Christiane and Schiele, Miriam A. and Mann, Julia and Geiger, Maximilian J. and Schartner, Christoph and Homola, Gy{\"o}rgy A. and Alpers, Georg W. and B{\"u}chel, Christian and Fehm, Lydia and Fydrich, Thomas and Gerlach, Alexander L. and Gloster, Andrew T. and Helbig-Lang, Sylvia and Kalisch, Raffael and Kircher, Tilo and Lang, Thomas and Lonsdorf, Tina B. and Pan{\´e}-Farr{\´e}, Christiane A. and Str{\"o}hle, Andreas and Weber, Heike and Zwanzger, Peter and Arolt, Volker and Romanos, Marcel and Wittchen, Hans-Ulrich and Hamm, Alfons and Pauli, Paul and Reif, Andreas and Deckert, J{\"u}rgen and Neufang, Susanne and H{\"o}fler, Michael and Domschke, Katharina},
  title     = {Orexin in the anxiety spectrum: association of a HCRTR1 polymorphism with panic disorder/agoraphobia, CBT treatment response and fear-related intermediate phenotypes},
  series = {Translational Psychiatry},
  volume    = {9},
  journal   = {Translational Psychiatry},
  doi       = {10.1038/s41398-019-0415-8},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-227479},
  year      = {2019},
  abstract  = {Preclinical studies point to a pivotal role of the orexin 1 (OX1) receptor in arousal and fear learning and therefore suggest the HCRTR1 gene as a prime candidate in panic disorder (PD) with/without agoraphobia (AG), PD/AG treatment response, and PD/AG-related intermediate phenotypes. Here, a multilevel approach was applied to test the non-synonymous HCRTR1 C/T Ile408Val gene variant (rs2271933) for association with PD/AG in two independent case-control samples (total n = 613 cases, 1839 healthy subjects), as an outcome predictor of a six-weeks exposure-based cognitive behavioral therapy (CBT) in PD/AG patients (n = 189), as well as with respect to agoraphobic cognitions (ACQ) (n = 483 patients, n = 2382 healthy subjects), fMRI alerting network activation in healthy subjects (n = 94), and a behavioral avoidance task in PD/AG pre- and post-CBT (n = 271). The HCRTR1 rs2271933 T allele was associated with PD/AG in both samples independently, and in their meta-analysis (p = 4.2 × 10-7), particularly in the female subsample (p = 9.8 × 10-9). T allele carriers displayed a significantly poorer CBT outcome (e.g., Hamilton anxiety rating scale: p = 7.5 × 10-4). The T allele count was linked to higher ACQ sores in PD/AG and healthy subjects, decreased inferior frontal gyrus and increased locus coeruleus activation in the alerting network. Finally, the T allele count was associated with increased pre-CBT exposure avoidance and autonomic arousal as well as decreased post-CBT improvement. In sum, the present results provide converging evidence for an involvement of HCRTR1 gene variation in the etiology of PD/AG and PD/AG-related traits as well as treatment response to CBT, supporting future therapeutic approaches targeting the orexin-related arousal system.},
  language  = {en}
}
@article{GiampaoloWojcikKleinHesslingetal.2019,
  author    = {Giampaolo, Sabrina and W{\´o}jcik, Gabriela and Klein-Hessling, Stefan and Serfling, Edgar and Patra, Amiya K.},
  title     = {B cell development is critically dependent on NFATc1 activity},
  series = {Cellular \& Molecular Immunology},
  volume    = {16},
  journal   = {Cellular \& Molecular Immunology},
  doi       = {10.1038/s41423-018-0052-9},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-233006},
  pages     = {508-520},
  year      = {2019},
  abstract  = {B cell development in bone marrow is a precisely regulated complex process. Through successive stages of differentiation, which are regulated by a multitude of signaling pathways and an array of lineage-specific transcription factors, the common lymphoid progenitors ultimately give rise to mature B cells. Similar to early thymocyte development in the thymus, early B cell development in bone marrow is critically dependent on IL-7 signaling. During this IL-7-dependent stage of differentiation, several transcription factors, such as E2A, EBF1, and Pax5, among others, play indispensable roles in B lineage specification and maintenance. Although recent studies have implicated several other transcription factors in B cell development, the role of NFATc1 in early B cell developmental stages is not known. Here, using multiple gene-manipulated mouse models and applying various experimental methods, we show that NFATc1 activity is vital for early B cell differentiation. Lack of NFATc1 activity in pro-B cells suppresses EBF1 expression, impairs immunoglobulin gene rearrangement, and thereby preBCR formation, resulting in defective B cell development. Overall, deficiency in NFATc1 activity arrested the pro-B cell transition to the pre-B cell stage, leading to severe B cell lymphopenia. Our findings suggest that, along with other transcription factors, NFATc1 is a critical component of the signaling mechanism that facilitates early B cell differentiation.},
  language  = {en}
}
@article{LetunicKhedkarBork2021,
  author    = {Letunic, Ivica and Khedkar, Supriya and Bork, Peer},
  title     = {SMART: recent updates, new developments and status in 2020},
  series = {Nucleic Acids Research},
  volume    = {49},
  journal   = {Nucleic Acids Research},
  number    = {D1},
  doi       = {10.1093/nar/gkaa937},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-363816},
  pages     = {D458-D460},
  year      = {2021},
  abstract  = {SMART (Simple Modular Architecture Research Tool) is a web resource (https://smart.embl.de) for the identification and annotation of protein domains and the analysis of protein domain architectures. SMART version 9 contains manually curatedmodels formore than 1300 protein domains, with a topical set of 68 new models added since our last update article (1). All the new models are for diverse recombinase families and subfamilies and as a set they provide a comprehensive overview of mobile element recombinases namely transposase, integrase, relaxase, resolvase, cas1 casposase and Xer like cellular recombinase. Further updates include the synchronization of the underlying protein databases with UniProt (2), Ensembl (3) and STRING (4), greatly increasing the total number of annotated domains and other protein features available in architecture analysis mode. Furthermore, SMART's vector-based protein display engine has been extended and updated to use the latest web technologies and the domain architecture analysis components have been optimized to handle the increased number of protein features available.},
  language  = {en}
}
@article{SchwabMeeuwsenEhlickeetal.2017,
  author    = {Schwab, Andrea and Meeuwsen, Annick and Ehlicke, Franziska and Hansmann, Jan and Mulder, Lars and Smits, Anthal and Walles, Heike and Kock, Linda},
  title     = {Ex vivo culture platform for assessment of cartilage repair treatment strategies},
  series = {ALTEX - Alternatives to animal experimentation},
  volume    = {34},
  journal   = {ALTEX - Alternatives to animal experimentation},
  number    = {2},
  doi       = {10.14573/altex.1607111},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-181665},
  pages     = {267-277},
  year      = {2017},
  abstract  = {There is a great need for valuable ex vivo models that allow for assessment of cartilage repair strategies to reduce the high number of animal experiments. In this paper we present three studies with our novel ex vivo osteochondral culture platform. It consists of two separated media compartments for cartilage and bone, which better represents the in vivo situation and enables supply of factors pecific to the different needs of bone and cartilage. We investigated whether separation of the cartilage and bone compartments and/or culture media results in the maintenance of viability, structural and functional properties of cartilage tissue. Next, we valuated for how long we can preserve cartilage matrix stability of osteochondral explants during long-term culture over 84 days. Finally, we determined the optimal defect size that does not show spontaneous self-healing in this culture system. It was demonstrated that separated compartments for cartilage and bone in combination with tissue-specific medium allow for long-term culture of osteochondral explants while maintaining cartilage viability, atrix tissue content, structure and mechanical properties for at least 56 days. Furthermore, we could create critical size cartilage defects of different sizes in the model. The osteochondral model represents a valuable preclinical ex vivo tool for studying clinically relevant cartilage therapies, such as cartilage biomaterials, for their regenerative potential, for evaluation of drug and cell therapies, or to study mechanisms of cartilage regeneration. It will undoubtedly reduce the number of animals needed for in vivotesting.},
  language  = {en}
}
@phdthesis{Broehl2024,
  author    = {Br{\"o}hl, Kathleen},
  title     = {„Lanfranks ‚Chirurgia parva' in der Abschrift Konrad Schrecks von Aschaffenburg" als Quelle zur sp{\"a}tmittelalterlich-fr{\"u}hneuzeitlichen Traumatologie},
  doi       = {10.25972/OPUS-35922},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-359227},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {Ziel der vorliegenden Arbeit ist es, „Lanfranks ‚Chirurgia parva' in der Abschrift Konrad Schrecks von Aschaffenburg"1 anhand der von Ralf Vollmuth in seiner Habilitationsschrift „Traumatologie und Feldchirurgie an der Wende vom Mittelalter zur Neuzeit" erarbeiteten Strukturvorgabe inhaltlich zu erschließen. Durch die Aufarbeitung verschiedener chirurgischer Fachb{\"u}cher und Manuale unter Verwendung einer gemeinsamen Strukturvorlage soll erm{\"o}glicht werden, medizinhistorische Quellen kritisch-kontrastiv zu vergleichen. Das bedeutet, dass die Quellen zuerst ediert und anschließend gegebenenfalls {\"u}bersetzt werden m{\"u}ssen. Im n{\"a}chsten Schritt werden die verwendeten Arzneimittel - pflanzlicher, tierischer, mineralischer Herkunft - identifiziert und bestimmt. Im Anschluss werden Monographien mit den bestimmenden Inhaltsstoffen und Eigenschaften erstellt. Anhand dieser Pflanzen- und Arzneistoffmonographien, die im Sinne einer Datenbank aufeinander aufbauen, sollte es dann m{\"o}glich sein, unter modernen pharmakologischen Gesichtspunkten die Wirksamkeit der verwendeten Arzneimittel zu erschließen. Eine ausreichende Zahl von Quellen, die nach einer gemeinsamen Strukturvorlage bearbeitet wurden, kann es schließlich erm{\"o}glichen, zu beurteilen, welche der beschriebenen Anwendungen repr{\"a}sentativ waren, welche Außenseiterstellung einnahmen oder nur theoretische Ans{\"a}tze bildeten, die praktisch keine Verwendung fanden.},
  subject      = {Lanfrancus, Mediolanensis},
  language  = {de}
}
@phdthesis{KellnergebFriedel2024,
  author    = {Kellner [geb. Friedel], Theresa},
  title     = {Suizid durch Selbstverbrennung im Freien - Eine bildmorphologische Analyse der Intensit{\"a}t und Verteilung von Verbrennungen im Zusammenhang mit der K{\"o}rperposition w{\"a}hrend des Brandgeschehens},
  doi       = {10.25972/OPUS-35919},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-359193},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {Ziel dieser Dissertation ist es, etwaige Gemeinsamkeiten und Unterschiede hinsichtlich der Distribution und Intensit{\"a}t von Brandverletzungen bei suizidaler Selbstverbrennung im Freien in Abh{\"a}ngigkeit von der jeweiligen K{\"o}rperposition zum Auffindezeitpunkt anhand der Aktenlage herauszuarbeiten. Das Studienkollektiv umfasst 38 F{\"a}lle aus 9 deutschen rechtsmedizinischen Instituten, darunter 13 (34,2 \%) weibliche und 25 (65,8 \%) m{\"a}nnliche Suizidenten/-innen im Alter von 18 - 77 Jahren. Neben einer deskriptiven visuellen Analyse erfolgt die Auswertung der Verteilung der Verbrennungen mittels der Software BurnCase 3D, die es erm{\"o}glicht, eine Sortierung der einzelnen K{\"o}rperbereiche nach deren durchschnittlicher Verbrennungsintensit{\"a}t innerhalb verschiedener Cluster f{\"u}r die unterschiedlichen Auffindepositionen am Tatort (R{\"u}ckenlage, Bauchlage, Seitenlage, Aufrecht, Sitzend) vorzunehmen. Am ehesten auf das in aufrechter Haltung beginnende Brandgeschehen zur{\"u}ckzuf{\"u}hren ist eine cluster{\"u}bergreifend auftretende, intensive und nach kranial an Intensit{\"a}t abnehmende Verbrennung des Halses sowie der lateralen und perioralen Kopfbereiche. Geringe Verbrennungsfolgen weisen die distalen unteren Extremit{\"a}ten sowie die Auflagefl{\"a}chen des K{\"o}rpers auf dem Untergrund auf. Es zeigt sich eine Beeinflussung der lokalen Verbrennungstiefe durch ein hohes Fettgewebevorkommen. Ebenfalls cluster{\"u}bergreifend k{\"o}nnen verst{\"a}rkte Brandwirkungen an den Oberschenkelinnenseiten festgestellt werden. In R{\"u}cken- und Bauchlage liegt zudem eine h{\"o}here Verbrennungsintensit{\"a}t an den Flanken, den Arminnenseiten und im Unterbauchbereich vor. Bei in Seitenlage verbrannten K{\"o}rpern ergeben sich Hinweise darauf, dass die nach oben gerichtete K{\"o}rperseite vermehrt Verbrennungen aufweist. In aufrechter und sitzender Position konzentriert sich der Brandfokus {\"u}berwiegend auf Torso, Hals und Kopf. Zus{\"a}tzlich wurde eine Betrachtung des Entstehungsmusters kutaner Hitzerisse durchgef{\"u}hrt. Hier ergaben sich {\"U}bereinstimmungen u.a. mit dem Verlauf der Hautfaltlinien nach Pinkus. Ein K{\"o}rperschema mit Abbildung der beobachteten Orientierungen der Risse wurde angefertigt. Die wichtigsten Limitationen ergeben sich aus einer geringen Fallzahl, einer fotografischen Dokumentation, die nicht alle K{\"o}rperbereiche in ausreichender Qualit{\"a}t und Detailliertheit abdeckt, sowie dem subjektiven Bias hinsichtlich der Bewertung der Verbrennungsintensit{\"a}ten.},
  subject      = {Selbstverbrennung},
  language  = {de}
}
@phdthesis{Landmesser2024,
  author    = {Landmesser, Patricia Sophia},
  title     = {Seropr{\"a}valenz von SARS-CoV-2 Antik{\"o}rpern bei Medizinstudierenden im zweiten klinischen Semester von Juli 2020 bis Juni 2021},
  doi       = {10.25972/OPUS-35924},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-359246},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {Im sechsten Semester des Medizinstudiums an der Julius-Maximilians-Universit{\"a}t W{\"u}rzburg findet das verpflichtende Praktikum „Impfkurs" statt. Im Rahmen dieses Kurses wurde vom Sommersemester 2020 bis zum Sommersemester 2021 ein standardisierter online Fragebogen erhoben, der unter anderem demographische Daten sowie Expositionsm{\"o}glichkeiten gegen{\"u}ber SARS-CoV-2 im privaten, beruflichen und universit{\"a}ren Umfeld erfragte. Zus{\"a}tzlich wurde im gleichen Zeitraum der SARS-CoV-2 Serostatus der Medizinstudierenden erhoben und ausgewertet und dieser mit den Daten des Fragebogens zusammengef{\"u}hrt. Daf{\"u}r wurden Blutproben entnommen, welche im Labor des Instituts f{\"u}r Virologie der Universit{\"a}t W{\"u}rzburg mittels Western Blot auf IgG/IgM/IgA Antik{\"o}rper gegen SARS-CoV-2 untersucht wurden.},
  subject      = {SARS-CoV-2},
  language  = {de}
}