@article{DannerKellerHaerteletal.2017, author = {Danner, Nadja and Keller, Alexander and H{\"a}rtel, Stephan and Steffan-Dewenter, Ingolf}, title = {Honey bee foraging ecology: Season but not landscape diversity shapes the amount and diversity of collected pollen}, series = {PLoS ONE}, volume = {12}, journal = {PLoS ONE}, number = {8}, doi = {10.1371/journal.pone.0183716}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-170424}, pages = {e0183716}, year = {2017}, abstract = {The availability of pollen in agricultural landscapes is essential for the successful growth and reproduction of honey bee colonies (Apis mellifera L.). The quantity and diversity of collected pollen can influence the growth and health of honey bee colonies, but little is known about the influence of landscape structure on pollen diet. In a field experiment, we rotated 16 honey bee colonies across 16 agricultural landscapes, used traps to collect samples of collected pollen and observed intra-colonial dance communication to gain information about foraging distances. DNA metabarcoding was applied to analyze mixed pollen samples. Neither the amount of collected pollen nor pollen diversity was related to landscape diversity. However, we found a strong seasonal variation in the amount and diversity of collected pollen in all sites independent of landscape diversity. The observed increase in foraging distances with decreasing landscape diversity suggests that honey bees compensated for lower landscape diversity by increasing their pollen foraging range in order to maintain pollen amount and diversity. Our results underscore the importance of a diverse pollen diet for honey bee colonies. Agri-environmental schemes aiming to support pollinators should focus on possible spatial and temporal gaps in pollen availability and diversity in agricultural landscapes.}, language = {en} } @article{KadeBakirciTandonetal.2022, author = {Kade, Juliane C. and Bakirci, Ezgi and Tandon, Biranche and Gorgol, Danila and Mrlik, Miroslav and Luxenhofer, Robert and Dalton, Paul D.}, title = {The Impact of Including Carbonyl Iron Particles on the Melt Electrowriting Process}, series = {Macromolecular Materials and Engineering}, volume = {307}, journal = {Macromolecular Materials and Engineering}, number = {12}, issn = {1438-7492}, doi = {10.1002/mame.202200478}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-318482}, year = {2022}, abstract = {Melt electrowriting, a high-resolution additive manufacturing technique, is used in this study to process a magnetic polymer-based blend for the first time. Carbonyl iron (CI) particles homogenously distribute into poly(vinylidene fluoride) (PVDF) melts to result in well-defined, highly porous structures or scaffolds comprised of fibers ranging from 30 to 50 µm in diameter. This study observes that CI particle incorporation is possible up to 30 wt\% without nozzle clogging, albeit that the highest concentration results in heterogeneous fiber morphologies. In contrast, the direct writing of homogeneous PVDF fibers with up to 15 wt\% CI is possible. The fibers can be readily displaced using magnets at concentrations of 1 wt\% and above. Combined with good viability of L929 CC1 cells using Live/Dead imaging on scaffolds for all CI concentrations indicates that these formulations have potential for the usage in stimuli-responsive applications such as 4D printing.}, language = {en} } @article{SchmidtSticherlingSardyetal.2020, author = {Schmidt, Enno and Sticherling, Michael and S{\´a}rdy, Mikl{\´o}s and Eming, R{\"u}diger and Goebeler, Matthias and Hertl, Michael and Hofmann, Silke C. and Hunzelmann, Nicolas and Kern, Johannes S. and Kramer, Harald and Nast, Alexander and Orzechowski, Hans-Dieter and Pfeiffer, Christiane and Schuster, Volker and Sitaru, Cassian and Zidane, Miriam and Zillikens, Detlef and Worm, Margitta}, title = {S2k guidelines for the treatment of pemphigus vulgaris/foliaceus and bullous pemphigoid: 2019 update}, series = {JDDG: Journal der Deutschen Dermatologischen Gesellschaft}, volume = {18}, journal = {JDDG: Journal der Deutschen Dermatologischen Gesellschaft}, number = {5}, doi = {10.1111/ddg.14097}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-217806}, pages = {516 -- 526}, year = {2020}, language = {en} } @techreport{SavvidisRothTutsch2022, type = {Working Paper}, author = {Savvidis, Dimitrios and Roth, Robert and Tutsch, Dietmar}, title = {Static Evaluation of a Wheel-Topology for an SDN-based Network Usecase}, series = {W{\"u}rzburg Workshop on Next-Generation Communication Networks (WueWoWas'22)}, journal = {W{\"u}rzburg Workshop on Next-Generation Communication Networks (WueWoWas'22)}, doi = {10.25972/OPUS-28071}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-280715}, pages = {3}, year = {2022}, abstract = {The increased occurrence of Software-Defined-Networking (SDN) not only improves the dynamics and maintenance of network architectures, but also opens up new use cases and application possibilities. Based on these observations, we propose a new network topology consisting of a star and a ring topology. This hybrid topology will be called wheel topology in this paper. We have considered the static characteristics of the wheel topology and compare them with known other topologies.}, subject = {Datennetz}, language = {en} } @book{OPUS4-18818, title = {MUS-IC-ON! Klang der Antike. Begleitband zur Ausstellung im Martin von Wagner Museum der Universit{\"a}t W{\"u}rzburg 10. Dezember 2019 bis 12. Juli 2020}, editor = {Leitmeir, Florian and Shehata, Dahlia and Wiener, Oliver}, edition = {1. Auflage}, publisher = {W{\"u}rzburg University Press}, address = {W{\"u}rzburg}, isbn = {978-3-95826-122-8}, doi = {10.25972/WUP-978-3-95826-123-5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-188181}, publisher = {W{\"u}rzburg University Press}, pages = {XIX, 221}, year = {2019}, abstract = {"MUS-IC-ON! Klang der Antike" ist der Begleitband zur gleichnamigen Sonderausstellung im Martin von Wagner-Museum W{\"u}rzburg (10. Dezember 2019 bis 12. Juli 2020). Die eigene Musik zu verstehen verlangt auch, nach Kl{\"a}ngen und Musik der Vergangenheit zu fragen. So offenbart der Blick auf antike Musikkulturen - des Vorderen Orients, {\"A}gyptens, Griechenlands und Roms - dem Betrachter kulturelle Konstanten, deren Verm{\"a}chtnis sich in unserer abendl{\"a}ndischen Musik erh{\"a}lt. Ziel des Begleitbands zur Ausstellung "MUS-IC-ON! Klang der Antike" ist es, die Relevanz musikhistorischer und -arch{\"a}ologischer Forschung f{\"u}r das Verst{\"a}ndnis der eigenen Musikkultur aufzuzeigen. An vier Schwerpunkten werden die Inhalte, Methoden und der Stand der Erforschung antiker Musik von international namhaften Wissenschaftler*innen in einer umfassenden und dennoch allgemein verst{\"a}ndlichen Weise vorgestellt. Der reichhaltig bebilderte Band ist damit als ein einf{\"u}hrendes und informatives Handbuch konzipiert, das {\"u}ber die Ausstellung hinaus von fachfremden Wissenschaftlern, Studierenden und interessierten Laien konsultiert wird. 1. Vom arch{\"a}ologischen Artefakt zum klingenden Instrument: Grundlage jedweder Erforschung antiker Musik ist die Rekonstruktion seiner Klangvielfalt. Unz{\"a}hlige Funde originaler Musikinstrumente, darunter vorderasiatische Kastenleiern, alt{\"a}gyptische Trompeten aus dem Grab des Tutanchamun oder die griechisch-r{\"o}mische Hydraulis, er{\"o}ffnen einen Weg, den Kl{\"a}ngen antiker Musik nachzugehen. Insgesamt sechs Beitr{\"a}ge mit einem historischen Rahmen, der von der Steinzeit bis in die r{\"o}mische Kaiserzeit reicht, stellen die Vorgehensweise aber auch die Herausforderungen bei der Bergung, Erforschung und dem Nachbau antiker Musikinstrumente vor. 2. Musik und Klang in Bild und Text: Ein umfassendes Bild vom Einsatz, der Spielweise, der Verbreitung und Entwicklung antiker Musikinstrumente liefern antike Bilder und Texte. Trotz der Vielfalt an Objekten, darunter griechische Vasen, assyrische Reliefbilder oder r{\"o}mische Mosaike, bedarf es einer analytischen und kritischen Herangehensweise bei der Analyse und Auswertung solcher Daten. Vorgestellt werden in diesem Themenschwerpunkt auch antike Notationsformen und Stimmungssysteme, die sich auf Papyri und Keilschrifttafeln erhalten haben, sowie die Schwierigkeiten ihrer Entzifferung. 3. Musikleben in der Antike: Wesentlich f{\"u}r das Verst{\"a}ndnis antiker Musik ist die Kenntnis ihres Einsatzes und ihres Umfeldes. Getrennt nach den verschiedenen Kulturkreisen stellen in diesem Kapitel insgesamt neun Autoren unterschiedliche Bereiche und Funktionen des Musizierens vor. Herausragend ist hier die Rolle von Musik im t{\"a}glichen Tempelkult, {\"u}ber die sich die in der Antike vorgestellte Macht von Musik aufzeigen l{\"a}sst, die sogar auf die Gem{\"u}ter der G{\"o}tter Einfluss zu nehmen vermag. Zus{\"a}tzlich aufschlussreich ist das Wissen von Ausbildung und Aufstieg auch namentlich bekannter Musiker, zumeist Hofmusiker, die den Ruhm ihres K{\"o}nigs verk{\"u}nden, aber auch regelrechte Virtuosen, die sich beispielsweise in antiken Wettstreiten hervortun, den musischen Agonen. 4. Kontinuit{\"a}t und Interkulturalit{\"a}t antiker Musikkulturen: Dieser Teil widmet sich Spuren, die antike Musikkulturen in der abendl{\"a}ndischen sowie in orientalischen Kulturr{\"a}umen hinterlassen haben. So geht unser modernes Tonsystem auf griechische, ja sogar auf babylonische Tonleitern zur{\"u}ck. Vorl{\"a}ufer der europ{\"a}ischen Kirchenorgel ist die Hydraulis, eine griechische Erfindung aus dem 3. vorchristlichen Jahrhundert. Viele vor {\"u}ber 4500 Jahren zwischen Euphrat und Tigris entwickelte Musikinstrumente werden noch heute im arabischen und afrikanischen Kulturkreis, ja selbst in nord- und osteurop{\"a}ischen L{\"a}ndern gespielt. Hervorgehoben werden außerdem historische Momente, die einen wesentlichen Einfluss auf die Entwicklung moderner Musiksysteme ausge{\"u}bt haben. Die Autoren: Benedetta Bellucci (Vorderasiatische Arch{\"a}ologie, Mainz), Arndt A. Both (Altamerikanistik, Musikarch{\"a}ologie, DAI Berlin), Ricardo Eichmann (Vorderasiatische Arch{\"a}ologie, DAI Berlin), Uri Gabbay (Altorientalistik, Jerusalem), Ralf Gehler (Instrumentenbauer, Schwerin), Carolin Goll (Martin von Wagner-Museum, W{\"u}rzburg), Jochen Griesbach (Martin von Wagner-Museum, Klassische Arch{\"a}ologie, W{\"u}rzburg), Stefan Hagel (Klassische Philologie, {\"O}AW Wien), Katharina Hepp ({\"A}gyptologie, W{\"u}rzburg), Peter Holmes (Instrumentenbauer, London), Marie Klein (Altorientalisik, W{\"u}rzburg), Carola Koch {\"A}gyptologie, W{\"u}rzburg), Ulrich Konrad (Historische Musikwissenschaft, W{\"u}rzburg), Eva Kurz ({\"A}gyptologie W{\"u}rzburg), Florian Leitmeir (Klassische Arch{\"a}ologie, W{\"u}rzburg), Thomas Ludewig (Klassische Arch{\"a}ologie, W{\"u}rzburg), Sam Mirelman (Altorientalistik, London), Daniel Schwemer (Altorientalistik, W{\"u}rzburg), Dahlia Shehata (Altorientalisik, W{\"u}rzburg), Martin Stadler ({\"A}gyptologie, W{\"u}rzburg), Olga Sutkowska (Kulturgeschicht der Antike, {\"O}AW Wien), G{\"u}nther E. Th{\"u}ry (Provinzialr{\"o}mische Arch{\"a}ologie, Salzburg), Marc Wahl (Numismatik, Wien/W{\"u}rzburg), Oliver Wiener (Historische Musikwissenschaft, W{\"u}rzburg), Nele Ziegler (Altorientalistik, Paris)}, subject = {Martin-von-Wagner-Museum. {\"A}ltere Abteilung}, language = {de} } @book{Arnold2018, author = {Arnold, Irina}, title = {Hunde auf ihrem Weg durch EUropa. Ethnographische Einblicke in den Tierschutz zwischen Spanien und Deutschland.}, doi = {10.25972/OPUS-17219}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-172193}, publisher = {Universit{\"a}t W{\"u}rzburg}, pages = {156}, year = {2018}, abstract = {Wie funktioniert Tierschutz im Alltag? Basierend auf Interviews und Feldforschung mit einem Verein, der Hunde aus spanischen T{\"o}tungsstationen nach Deutschland holt und in neue Familien vermittelt, wird den vielf{\"a}ltigen Aspekten dieser Frage aus Sicht der Europ{\"a}ischen Ethnologie nachgegangen. Das Beispiel des Welpen „Hugo", der w{\"a}hrend der Forschung gefunden wurde, veranschaulicht die allt{\"a}glichen Praktiken der Tierschutzarbeit. Es dient außerdem als Ausgangspunkt f{\"u}r die Beschreibung der komplexen Netzwerke, in die der Verein und seine Akteur_innen eingebunden sind. Netzwerke, hier konzeptualisiert als Assemblages, bestehen nicht nur aus Menschen. Sie umfassen ebenfalls nichtmenschliche Tiere, Gesetze, Dinge, Institutionen, Diskurse und Erz{\"a}hlungen. Die qualitativen ethnographischen Einblicke in das Allt{\"a}gliche der Tierschutzarbeit werden gerahmt, begleitet und gest{\"u}tzt durch Ausf{\"u}hrungen zur Tierschutz- und Tierrechtsgeschichte. Außerdem gibt die Arbeit einen {\"U}berblick {\"u}ber Perspektiven auf nichtmenschliche Tiere aus verschiedenen wissenschaftlichen Disziplinen wie der Philosophie, den Natur- und Rechtswissenschaften. Die Bereicherungen einer europ{\"a}isch-ethnologisch ausgerichteten Forschung, die mit und nicht nur {\"u}ber andere Lebewesen forscht, werden in dieser Arbeit herausgestellt.}, subject = {Tierschutz}, language = {de} } @book{JobFliessbachSchendzielorzBittlingmaieretal.2019, author = {Job, Hubert and Fließbach-Schendzielorz, Maike and Bittlingmaier, Sarah and Herling, Anne and Woltering, Manuel}, title = {Akzeptanz der bayerischen Nationalparks - Ein Beitrag zum sozio{\"o}konomischen Monitoring in den Nationalparks Bayerischer Wald und Berchtesgaden}, edition = {1. Auflage}, publisher = {W{\"u}rzburg University Press}, address = {W{\"u}rzburg}, isbn = {978-3-95826-102-0}, issn = {0510-9833}, doi = {10.25972/WUP-978-3-95826-103-7}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-171246}, publisher = {W{\"u}rzburg University Press}, pages = {XI, 149}, year = {2019}, abstract = {Nationalparks sind das {\"a}lteste und bekannteste fl{\"a}chenbezogene Naturschutzinstrument weltweit. F{\"u}r den Erhalt einer nachhaltigen Lebensgrundlage und die Entwicklung der Biodiversit{\"a}t sowie f{\"u}r mehr Naturdynamik in der Landschaft haben sie eine sehr große Bedeutung, auch in unseren Breiten. Dennoch ist die Einstellung zu Nationalparks von Seiten der unmittelbaren Anwohner nicht immer unproblematisch. Entsprechend versucht die vorliegende wissenschaftliche Analyse neue Erkenntnisse bez{\"u}glich der Akzeptanz der Nationalparks Bayerischer Wald und Berchtesgaden, den {\"a}ltesten Deutschlands, aufzuzeigen. Empirische Grundlagen f{\"u}r diese Studie sind eine bayernweite Online-Befragung, qualitative Experteninterviews und aufw{\"a}ndige repr{\"a}sentative schriftliche Befragungen in den Nationalpark-Landkreisen Regen und Freyung-Grafenau bzw. Berchtesgadener Land im Jahr 2018. Auch die zeitliche Entwicklung der Akzeptanz wird auf Basis der Ergebnisse von Vorg{\"a}ngerstudien, soweit m{\"o}glich, ber{\"u}cksichtigt. Dabei sind es {\"o}konomische, emotionale, interpersonelle, soziokulturelle und nicht zuletzt f{\"u}r Geographen besonders interessante raumzeitliche Pr{\"a}diktoren der Akzeptanz beider Nationalparks, die im Fokus der Untersuchungen stehen.}, subject = {Nationalpark Bayerischer Wald}, language = {de} } @book{StaffeldtThieroff2020, author = {Staffeldt, Sven and Thieroff, Rolf}, title = {Oberfl{\"a}chengrammatischer Wald : Syntaktische Baumschule am Beispiel eines authentischen Textes}, edition = {1. Auflage}, isbn = {978-3-945459-31-7}, doi = {10.25972/OPUS-20561}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-205614}, publisher = {Universit{\"a}t W{\"u}rzburg}, pages = {150}, year = {2020}, abstract = {When analysing a sentence, you are revealing your understanding of this sentence by certain criteria. Before analysing a sentence, you need to understand it in a basic, pre-analytical, concealed way: Analysis is not possible without understanding. The process of analysing a sentence will concretize and finalize this understanding. You will need a theoretical background, the theoretical "tools" when uncovering your syntactical understanding of a sentence by means of syntactical analysis: Analysis is not possible without these theoretical tools. The tools used in the theoretical framework of surface grammar (Oberfl{\"a}chengrammatik) as they were first elaborated by Eisenberg in his 1986 grammar book include syntactic constituents such as verb, noun, noun group and the like (syntactic forms), and syntactic relations, such as predicate, subject, object and the like (syntactic functions). While this sounds like a rather traditional view of grammar, the thorough analyses presented here show that there is more to surface grammar than one might expect. The prime goal of this publication is to present the results of different sentence analyses in form of syntactical trees with information about the forms and functions of the syntactic constituents used. You will find more than 100 syntactical trees, forming a "syntactical forest". It gives students (and other readers) who are analysing sentences in the framework of surface grammar an opportunity to test their knowledge and understanding of certain syntactical phenomena against the background of authentic use of speech. Besides, the "Surface Grammar in action" is proof of the soundness of the analytical methods and tools used by appropriately analysing linguistic phenomena found in the wilderness of journalistic text production. And yet, sometimes there is more than one solution, more than just one way to explain the structures found. Most authors decide which road to take by themselves. We include the crossways by adding our dialogues about arguable cases, so that readers may see several options of how to explain the more difficult (and more interesting) aspects of grammar. The present publication appears in the year of Peter Eisenberg's 80th birthday and is dedicated to him with the deepest respect for his life work and especially for the foundation of a syntactic framework with which so many generations of university students are working and which has helped so many understand the intriguing features of the grammar of the German language.}, subject = {Grammatik}, language = {de} } @article{ZieglerPollingerBoelletal.2020, author = {Ziegler, Katrin and Pollinger, Felix and B{\"o}ll, Susanne and Paeth, Heiko}, title = {Statistical modeling of phenology in Bavaria based on past and future meteorological information}, series = {Theoretical and Applied Climatology}, volume = {140}, journal = {Theoretical and Applied Climatology}, issn = {0177-798X}, doi = {10.1007/s00704-020-03178-4}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-232717}, pages = {1467-1481}, year = {2020}, abstract = {Plant phenology is well known to be affected by meteorology. Observed changes in the occurrence of phenological phases arecommonly considered some of the most obvious effects of climate change. However, current climate models lack a representationof vegetation suitable for studying future changes in phenology itself. This study presents a statistical-dynamical modelingapproach for Bavaria in southern Germany, using over 13,000 paired samples of phenological and meteorological data foranalyses and climate change scenarios provided by a state-of-the-art regional climate model (RCM). Anomalies of severalmeteorological variables were used as predictors and phenological anomalies of the flowering date of the test plantForsythiasuspensaas predictand. Several cross-validated prediction models using various numbers and differently constructed predictorswere developed, compared, and evaluated via bootstrapping. As our approach needs a small set of meteorological observationsper phenological station, it allows for reliable parameter estimation and an easy transfer to other regions. The most robust andsuccessful model comprises predictors based on mean temperature, precipitation, wind velocity, and snow depth. Its averagecoefficient of determination and root mean square error (RMSE) per station are 60\% and ± 8.6 days, respectively. However, theprediction error strongly differs among stations. When transferred to other indicator plants, this method achieves a comparablelevel of predictive accuracy. Its application to two climate change scenarios reveals distinct changes for various plants andregions. The flowering date is simulated to occur between 5 and 25 days earlier at the end of the twenty-first century comparedto the phenology of the reference period (1961-1990).}, language = {en} } @article{LangePohlmannRother2020, author = {Lange, Sarah D{\´e}sir{\´e}e and Pohlmann-Rother, Sanna}, title = {{\"U}berzeugungen von Grundschullehrkr{\"a}ften zum Umgang mit nicht-deutschen Erstsprachen im Unterricht}, series = {Zeitschrift f{\"u}r Bildungsforschung}, volume = {10}, journal = {Zeitschrift f{\"u}r Bildungsforschung}, issn = {2190-6890}, doi = {10.1007/s35834-020-00265-4}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-232705}, pages = {43-60}, year = {2020}, abstract = {Mit der vorliegenden Studie werden die {\"U}berzeugungen von berufst{\"a}tigen Grundschullehrkr{\"a}fte zum Umgang mit nicht-deutschen Erstsprachen im Unterricht untersucht und die Bedeutung formaler und informeller bzw. non-formaler Lerngelegenheiten f{\"u}r diese {\"U}berzeugungen analysiert. Die Ergebnisse der Fragebogenstudie (N = 123) zeigen, dass die Mehrheit der befragten Lehrkr{\"a}fte davon {\"u}berzeugt ist, dass Erstsprachen zumindest zeitweise einen Platz in ihrem Unterricht haben sollten. So stimmen beispielsweise 75 \% der befragten Lehrkr{\"a}fte der Aussage mindestens teilweise zu, dass die Sch{\"u}lerinnen und Sch{\"u}ler von Zeit zu Zeit Lerninhalte in ihren Erstsprachen besprechen d{\"u}rfen. Dem Einsatz von nicht-deutschen Lernmaterialien im Unterricht stehen knapp 60 \% der Lehrkr{\"a}fte mindestens positiv gegen{\"u}ber. Die multiplen Regressionsanalysen zeigen, dass sich die erstsprachenintegrierenden {\"U}berzeugungen anhand der Nutzung von formalen und informellen bzw. non-formalen Lerngelegenheiten teilweise erkl{\"a}ren lassen. Eine formale Aus- und Weiterbildung im Themenbereich des Deutschen als Zweitsprache hat einen positiven Einfluss auf die {\"U}berzeugungen von Grundschullehrkr{\"a}ften zum Einbezug von Erstsprachen in ihren Unterricht. Zudem sind es auch informelle bzw. non-formale Sprachkontakte (wie etwa Alltagskommunikation oder Mediennutzung in einer Fremdsprache), deren Nutzung die {\"U}berzeugungen der Grundschullehrkr{\"a}fte hinsichtlich des Umgangs mit Erstsprachen im Unterricht beeinflussen. Unterricht beeinflussen}, language = {de} } @article{MoratinThoeleLangetal.2023, author = {Moratin, Helena and Th{\"o}le, Anna and Lang, Josephine and Ehret Kasemo, Totta and St{\"o}th, Manuel and Hagen, Rudolf and Scherzad, Agmal and Hackenberg, Stephan}, title = {Ag- but not ZnO-nanoparticles disturb the airway epithelial barrier at subtoxic concentrations}, series = {Pharmaceutics}, volume = {15}, journal = {Pharmaceutics}, number = {10}, issn = {1999-4923}, doi = {10.3390/pharmaceutics15102506}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357403}, year = {2023}, abstract = {Inhalation is considered to be the most relevant source of human exposure to nanoparticles (NPs); however, only a few investigations have addressed the influence of exposing the respiratory mucosal barrier to subcytotoxic doses. In the nasal respiratory epithelium, cells of the mucosa represent one of the first contact points of the human organism with airborne NPs. Disruption of the epithelial barrier by harmful materials can lead to inflammation in addition to potential intrinsic toxicity of the particles. The aim of this study was to investigate whether subtoxic concentrations of zinc oxide (ZnO)- and silver (Ag)-NPs have an influence on upper airway barrier integrity. Nasal epithelial cells from 17 donors were cultured at the air-liquid interface and exposed to ZnO- and Ag-NPs. Barrier function, quantified by transepithelial electrical resistance (TEER), decreased after treatment with 10 µg/mL Ag-NPs, but FITC-dextran permeability remained stable and no change in mRNA levels of tight junction proteins and E-cadherin was detected by real-time quantitative PCR (RT-qPCR). The results indicate that subtoxic concentrations of Ag-NPs may already induce damage of the upper airway epithelial barrier in vitro. The lack of similar disruption by ZnO-NPs of similar size suggests a specific effect by Ag-NPs.}, language = {en} } @article{IsraelRiehlButtetal.2023, author = {Israel, Ina and Riehl, Gabriele and Butt, Elke and Buck, Andreas K. and Samnick, Samuel}, title = {Gallium-68-labeled KISS1-54 peptide for mapping KISS1 receptor via PET: initial evaluation in human tumor cell lines and in tumor-bearing mice}, series = {Pharmaceuticals}, volume = {17}, journal = {Pharmaceuticals}, number = {1}, issn = {1424-8247}, doi = {10.3390/ph17010044}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-355898}, year = {2023}, abstract = {Kisspeptins (KPs, KISS1) and their receptor (KISS1R) play a pivotal role as metastasis suppressor for many cancers. Low or lost KP expression is associated with higher tumor grade, increased metastatic potential, and poor prognosis. Therefore, KP expression has prognostic relevance and correlates with invasiveness in cancers. Furthermore, KISS1R represents a very promising target for molecular imaging and therapy for KISS1R-expressing tumors. The goal of this study was to evaluate the developed KISS1-54 derivative, [\(^{68}\)Ga]KISS1-54, as a PET-imaging probe for KISS1R-expressing tumors. The NODAGA-KISS1-54 peptide was labeled by Gallium-68, and the stability of the resulting [\(^{68}\)Ga]KISS1-54 evaluated in injection solution and human serum, followed by an examination in different KISS1R-expressing tumor cell lines, including HepG2, HeLa, MDA-MB-231, MCF7, LNCap, SK-BR-3, and HCT116. Finally, [\(^{68}\)Ga]KISS1-54 was tested in LNCap- and MDA-MB-231-bearing mice, using µ-PET, assessing its potential as an imaging probe for PET. [\(^{68}\)Ga]KISS1-54 was obtained in a 77 ± 7\% radiochemical yield and at a >99\% purity. The [\(^{68}\)Ga]KISS1-54 cell uptake amounted to 0.6-4.4\% per 100,000 cells. Moreover, the accumulation of [\(^{68}\)Ga]KISS1-54 was effectively inhibited by nonradioactive KISS1-54. In [\(^{68}\)Ga]KISS1-54-PET, KISS1R-positive LNCap-tumors were clearly visualized as compared to MDA-MB-231-tumor implant with predominantly intracellular KISS1R expression. Our first results suggest that [\(^{68}\)Ga]KISS1-54 is a promising candidate for a radiotracer for targeting KISS1R-expressing tumors via PET.}, language = {en} } @article{OdorferVolkmann2023, author = {Odorfer, Thorsten M. and Volkmann, Jens}, title = {Deep brain stimulation for focal or segmental craniocervical dystonia in patients who have failed botulinum neurotoxin therapy - a narrative review of the literature}, series = {Toxins}, volume = {15}, journal = {Toxins}, number = {10}, issn = {2072-6651}, doi = {10.3390/toxins15100606}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357707}, year = {2023}, abstract = {(1) Background: The first-line treatment for patients with focal or segmental dystonia with a craniocervical distribution is still the intramuscular injection of botulinum neurotoxin (BoNT). However, some patients experience primary or secondary treatment failure from this potential immunogenic therapy. Deep brain stimulation (DBS) may then be used as a backup strategy in this situation. (2) Methods: Here, we reviewed the current study literature to answer a specific question regarding the efficacy and safety of the use of DBS, particularly for cervical dystonia (CD) and Meige syndrome (MS) in patients with documented treatment failure under BoNT. (3) Results: There are only two studies with the highest level of evidence in this area. Despite this clear limitation, in the context of the narrowly defined research question of this paper, it is possible to report 161 patients with CD or MS who were included in studies that were able to show a statistically significant reduction in dystonic symptoms using DBS. Safety and tolerability data appeared adequate. However, much of the information is based on retrospective observations. (4) Conclusions: The evidence base in this area is in need of further scientific investigation. Most importantly, more randomized, controlled and double-blind trials are needed, possibly including a head-to-head comparison of DBS and BoNT.}, language = {en} } @phdthesis{Behne2024, author = {Behne, Robert Stefan Friedrich}, title = {Development Of A Human iPSC-Derived Cortical Neuron Model Of Adaptor- Protein-Complex-4-Deficiency}, doi = {10.25972/OPUS-35139}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-351390}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2024}, abstract = {Adaptor-protein-4-deficiency (AP-4-deficiency) is an autosomal-recessive childhood- onset form of complicated hereditary spastic paraplegia (HSP) caused by bi-allelic loss- of-function mutations in one of the four subunits of the AP-4-complex. These four conditions are named SPG47 (AP4B1, OMIM \#614066), SPG50 (AP4M1, OMIM \#612936), SPG51 (AP4E1, OMIM \#613744) and SPG52 (AP4S1, OMIM \#614067), respectively and all present with global developmental delay, progressive spasticity and seizures. Imaging features include a thinning of the corpus callosum, ventriculomegaly and white matter changes. AP-4 is a highly conserved heterotetrameric complex, which is responsible for polarized sorting of transmembrane cargo including the autophagy- related protein 9 A (ATG9A). Loss of any of the four subunits leads to an instable complex and defective sorting of AP-4-cargo. ATG9A is implicated in autophagosome formation and neurite outgrowth. It is missorted in AP-4-deficient cells and CNS-specific knockout of Atg9a in mice results in a phenotype reminiscent of AP-4-deficiency. However, the AP-4-related cellular phenotypes including ATG9A missorting have not been investigated in human neurons. Thus, the aim of this study is to provide the first human induced pluripotent stem cell- derived (iPSC) cortical neuron model of AP-4-deficiency to explore AP-4-related phenotypes in preparation for a high-content screening. Under the hypothesis that AP-4- deficiency leads to ATG9A missorting, elevated ATG9A levels, impaired autophagy and neurite outgrowth in human iPSC-derived cortical neurons, in vitro biochemical and imaging assays including automated high-content imaging and analysis were applied. First, these phenotypes were investigated in fibroblasts from three patients with compound heterozygous mutations in the AP4B1 gene and their sex-matched parental controls. The same cell lines were used to generate iPSCs and differentiate them into human excitatory cortical neurons. This work shows that ATG9A is accumulating in the trans-Golgi-network in AP-4- deficient human fibroblasts and that ATG9A levels are increased compared to parental controls and wild type cells suggesting a compensatory mechanism. Protein levels of the AP4E1-subunit were used as a surrogate marker for the AP-4-complex and were decreased in AP-4-deficient fibroblasts with co-immunoprecipitation confirming the instability of the complex. Lentiviral re-expression of the AP4B1-subunit rescues this corroborating the fact that a stable AP-4-complex is needed for ATG9A trafficking. Surprisingly, autophagic flux was present in AP-4-deficient fibroblasts under nutrient- rich and starvation conditions. These phenotypic markers were evaluated in iPSC-derived cortical neurons and here, a robust accumulation of ATG9A in the juxtanuclear area was seen together with elevated ATG9A protein levels. Strikingly, assessment of autophagy markers under nutrient-rich conditions showed alterations in AP-4-deficient iPSC- derived cortical neurons indicating dysfunctional autophagosome formation. These findings point towards a neuron-specific impairment of autophagy and need further investigation. Adding to the range of AP-4-related phenotypes, neurite outgrowth and branching are impaired in AP-4-deficient iPSC-derived cortical neurons as early as 24h after plating and together with recent studies point towards a distinct role of ATG9A in neurodevelopment independent of autophagy. Together, this work provides the first patient-derived neuron model of AP-4-deficiency and shows that ATG9A is sorted in an AP-4-dependent manner. It establishes ATG9A- related phenotypes and impaired neurite outgrowth as robust markers for a high-content screening. This disease model holds the promise of providing a platform to further study AP-4-deficiency and to search for novel therapeutic targets.}, subject = {Adaptorproteine}, language = {en} } @article{WatzlingKlausWeidemeieretal.2023, author = {Watzling, Martin and Klaus, Lorenz and Weidemeier, Tamara and Horder, Hannes and Ebert, Regina and Blunk, Torsten and Bauer-Kreisel, Petra}, title = {Three-dimensional breast cancer model to investigate CCL5/CCR1 expression mediated by direct contact between breast cancer cells and adipose-derived stromal cells or adipocytes}, series = {Cancers}, volume = {15}, journal = {Cancers}, number = {13}, issn = {2072-6694}, doi = {10.3390/cancers15133501}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-362502}, year = {2023}, abstract = {The tumor microenvironment (TME) in breast cancer is determined by the complex crosstalk of cancer cells with adipose tissue-inherent cells such as adipose-derived stromal cells (ASCs) and adipocytes resulting from the local invasion of tumor cells in the mammary fat pad. This leads to heterotypic cellular contacts between these cell types. To adequately mimic the specific cell-to-cell interaction in an in vivo-like 3D environment, we developed a direct co-culture spheroid model using ASCs or differentiated adipocytes in combination with MDA-MB-231 or MCF-7 breast carcinoma cells. Co-spheroids were generated in a well-defined and reproducible manner in a high-throughput process. We compared the expression of the tumor-promoting chemokine CCL5 and its cognate receptors in these co-spheroids to indirect and direct standard 2D co-cultures. A marked up-regulation of CCL5 and in particular the receptor CCR1 with strict dependence on cell-cell contacts and culture dimensionality was evident. Furthermore, the impact of direct contacts between ASCs and tumor cells and the involvement of CCR1 in promoting tumor cell migration were demonstrated. Overall, these results show the importance of direct 3D co-culture models to better represent the complex tumor-stroma interaction in a tissue-like context. The unveiling of tumor-specific markers that are up-regulated upon direct cell-cell contact with neighboring stromal cells, as demonstrated in the 3D co-culture spheroids, may represent a promising strategy to find new targets for the diagnosis and treatment of invasive breast cancer.}, language = {en} } @phdthesis{Stark2024, author = {Stark, Irmgard Katharina}, title = {Einfluss von Interferon auf das Infektionsverhalten von Herpes simplex Virus 1 und seiner DUB - Mutante C65A in der Zellkultur}, doi = {10.25972/OPUS-35195}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-351950}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2024}, abstract = {Die Erforschung viraler Proteine ist wichtig, um virale Infektionen besser verstehen und damit therapieren zu k{\"o}nnen. Die Aufkl{\"a}rung der DUB-Funktion auf dem viralen Herpesprotein pUL36 erm{\"o}glicht ein besseres Verst{\"a}ndnis des Infektionshergangs und k{\"o}nnte zur Entwicklung eines Enzyminhibitors f{\"u}hren, der nur an diesem Enzym ansetzt, nachdem es sich von den zellul{\"a}ren DUBs unterscheidet (Kattenhorn et al., 2005). In dieser Arbeit konnten die vorherigen Daten, die eine st{\"a}rkere Hemmung der DUB- Mutante unter Interferoneinfluss zeigten, in unterschiedlichen Assay-Designs best{\"a}tigt werden. Auch Versuche mit einem anderen Herpes simplex Virus Strang, best{\"a}tigten die vorherigen Daten. Die Ergebnisse zeigen, dass die DUB-Funktion f{\"u}r HSV-1 wichtig ist f{\"u}r die virale Evasion der zellul{\"a}ren Immunantwort. Die genaue Funktion der DUB in der Infektion ist jedoch unklar. Aufgrund der vorbestehenden Datenlage erschien am wahrscheinlichsten, dass die DUB-Funktion vor Eindringen des Herpes Simplex Virus in den Zellkern zum Tragen kommt, womit es nach Abnahme des Interferons nicht zu einer viralen Reaktivierung k{\"a}me. Deshalb wurden Untersuchungen unternommen, um eine m{\"o}gliche Reaktivierung nach Abnahme des Interferons n{\"a}her zu untersuchen. Hierf{\"u}r wurden zwei verschiedene Experimente entwickelt. Einmal wurde das Interferon direkt nach Infektion und einmal 3 Tage nach Infektion (3dpi) abgenommen. Die Ergebnisse zeigten beide eine st{\"a}rkere Hemmung der DUB-HSV-1-Mutante unter Interferoneinfluss. Bei Abnahme des Interferons direkt nach Infektion lag bei Wildtyp und Mutante ein leichter Anstieg der Plaquezahlen vor, wobei dieser Effekt von der Dosis des Interferons abh{\"a}ngig war. Eine hohe Interferondosis beg{\"u}nstigte bei beiden eine st{\"a}rkere Hemmung, allerdings bei beiden auch eine leichte Erh{\"o}hung der Plaquezahl nach Abnahme. Bei einer niedrigen Dosis konnte nur eine st{\"a}rkere Hemmung der DUB-Mutante, jedoch keine Reaktivierung bei Wildtyp und Mutante nach Abnahme des Interferons gezeigt werden. Bei Abnahme drei Tage nach Infektion zeigte sich sowohl bei dem Wildtyp-Virus als auch der DUB- Mutante kein Anstieg in den Plaquezahlen. Es sind, nachdem Deubiquitinierung nicht nur eine Rolle in der Verhinderung des proteosomalen Abbaus von in die Zelle eingedrungenem Virus spielt, sondern auch der Zellregulation, mehrere Szenarien denkbar, die diesen Ph{\"a}notyp erkl{\"a}ren k{\"o}nnten. Die DUB-Funktion k{\"o}nnte zwar den proteosomalen Abbau durch Deubiqutinierung und damit Verhinderung der Markierung des Virus zum zellul{\"a}ren Abbau verhindern. Allerdings k{\"o}nnten sich durch einen langsameren Transport aus der Zelle oder in den Nucleus auch weniger Plaques bei der Mutante als wie beim Wildtyp unter Interferoneinfluss bilden, nachdem das Virus dann leichter Ziel antiviraler Proteine werden k{\"o}nnte. Oder die DUB-Funktion spielt eine Rolle beim Eintritt in den Kern durch Modifikationen anderer Proteine. Virengenome k{\"o}nnten auch durch eine fehlende DUB-Funktion reprimiert werden oder die Zelle durch Apoptose absterben. Interessanterweise konnte keine Hemmung der DUB-Mutante in Interferon behandelten U-2 OS Zellen gezeigt werden, von denen ein Defekt im STING- vermittelten Signalweg bekannt ist. Vielleicht zeigt dies, dass das STING-Protein an dem gezeigten DUB-Ph{\"a}notyp beteiligt ist. Nachgewiesen ist außerdem bereits eine Funktion des Enzyms bei der zweiten Umh{\"u}llung der Kapside bei Pseudorabiesvirus (M{\"o}hl, 2011). Weitere Untersuchungen unter Einsatz bspw. von Immunfluoreszenz, Proteasominhibitoren oder weiteren Zelllinien wie Saos-2, sind n{\"o}tig, um die genaue Funktion zu kl{\"a}ren.}, subject = {Interferon}, language = {de} } @article{GuederReinFlohretal.2023, author = {G{\"u}der, G{\"u}lmisal and Rein, Eva von and Flohr, Thomas and Weismann, Dirk and Schmitt, Dominik and St{\"o}rk, Stefan and Frantz, Stefan and Kratzer, Vincent and Kendi, Christian}, title = {Motion detectors as additional monitoring devices in the intensive care unit — a proof-of-concept study}, series = {Applied Sciences}, volume = {13}, journal = {Applied Sciences}, number = {16}, issn = {2076-3417}, doi = {10.3390/app13169319}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-362404}, year = {2023}, abstract = {Background: Monitoring the vital signs of delirious patients in an intensive care unit (ICU) is challenging, as they might (un-)intentionally remove devices attached to their bodies. In mock-up scenarios, we systematically assessed whether a motion detector (MD) attached to the bed may help in identifying emergencies. Methods: We recruited 15 employees of the ICU and equipped an ICU bed with an MD (IRON Software GmbH, Gr{\"u}nwald, Germany). Participants were asked to replay 22 mock-up scenes of one-minute duration each: 12 scenes with movements and 10 without movements, of which 5 were emergency scenes ("lying dead-still, with no or very shallow breathing"). Blinded recordings were presented to an evaluation panel consisting of an experienced ICU nurse and a physician, who was asked to assess and rate the presence of motions. Results: Fifteen participants (nine women; 173 ± 7.0 cm; 78 ± 19 kg) joined the study. In total, 286 out of 330 scenes (86.7\%) were rated correctly. Ratings were false negative (FN: "no movements detected, but recorded") in 7 out of 180 motion scenes (3.9\%). Ratings were false positive (FP: "movements detected, but not recorded") in 37 out of 150 scenes (24.7\%), more often in men than women (26 out of 60 vs. 11 out of 90, respectively; p \< 0.001). Of note, in 16 of these 37 FP-rated scenes, a vibrating mobile phone was identified as a potential confounder. The emergency scenes were correctly rated in 64 of the 75 runs (85.3\%); 10 of the 11 FP-rated scenes occurred in male subjects. Conclusions: The MD allowed for identifying motions of test subjects with high sensitivity (96\%) and acceptable specificity (75\%). Accuracy might increase further if activities are recorded continuously under real-world conditions.}, language = {en} } @article{HiewEibeckNguemenietal.2023, author = {Hiew, Shawn and Eibeck, Leila and Nguemeni, Carine and Zeller, Daniel}, title = {The influence of age and physical activity on locomotor adaptation}, series = {Brain Sciences}, volume = {13}, journal = {Brain Sciences}, number = {9}, issn = {2076-3425}, doi = {10.3390/brainsci13091266}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-362478}, year = {2023}, abstract = {Background: Aging increases individual susceptibility to falls and injuries, suggesting poorer adaptation of balance responses to perturbation during locomotion, which can be measured with the locomotor adaptation task (LAT). However, it is unclear how aging and lifestyle factors affect these responses during walking. Hence, the present study investigates the relationship between balance and lifestyle factors during the LAT in healthy individuals across the adult lifespan using a correlational design. Methods: Thirty participants aged 20-78 years performed an LAT on a split-belt treadmill (SBT). We evaluated the magnitude and rate of adaptation and deadaptation during the LAT. Participants reported their lifelong physical and cognitive activity. Results: Age positively correlated with gait-line length asymmetry at the late post-adaptation phase (p = 0.007). These age-related effects were mediated by recent physical activity levels (p = 0.040). Conclusion: Our results confirm that locomotor adaptive responses are preserved in aging, but the ability to deadapt newly learnt balance responses is compromised with age. Physical activity mediates these age-related effects. Therefore, gait symmetry post-adaptation could effectively measure the risk of falling, and maintaining physical activity could protect against declines in balance.}, language = {en} } @phdthesis{Gabel2024, author = {Gabel, Martin Sebastian}, title = {Behavioural resistance to \(Varroa\) \(destructor\) in the Western honeybee \(Apis\) \(mellifera\) - Mechanisms leading to decreased mite reproduction}, doi = {10.25972/OPUS-36053}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-360536}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2024}, abstract = {The Western Honeybee (Apis mellifera) is among the most versatile species in the world. Its adaptability is rooted in thousands of the differently specialized individuals acting jointly together. Thus, bees that are able to handle a certain task or condition well can back up other individuals less capable to do so on the colony level. Vice versa, the latter individuals might perform better in other situations. This evolutionary recipe for success ensures the survival of colonies despite challenging habitat conditions. In this context, the ectoparasitic mite Varroa destructor reflects the most pronounced biotic challenge to honeybees worldwide. Without proper treatment, infested colonies rapidly dwindle and ultimately die. Nevertheless, resistance behaviours against this parasite have evolved in some populations through natural selection, enabling colonies to survive untreated. In this, different behaviours appear to be adapted to the respective habitat conditions and may complement each other. Yet, the why and how of this behavioural response to the mite remains largely unknown. My thesis focuses on the biological background of Varroa-resistance traits in honeybees and presents important findings for the comprehension of this complex host-parasite interaction. Based on this, I draw implications for both, applied bee breeding and scientific investigations in the field of Varroa-resistance. Specifically, I focus on two traits commonly found in resistant and, to a lower degree, also mite-susceptible colonies: decreased mite reproduction and the uncapping and subsequent recapping of sealed brood cells. Examining failures in the reproductive success of mites as a primary mechanism of Varroa-resistance, I was able to link them to specific bee behaviours and external factors. Since mite reproduction and the brood rearing of bees are inevitably connected, I first investigated the effects of brood interruption on the reproductive success of mites. Brood interruption decreased the reproductive success of mites both immediately and in the long term. By examining the causes of reproductive failure, I could show that this was mainly due to an increased share of infertile mites. Furthermore, I proved that interruption in brood rearing significantly increased the expression of recapping behaviour. These findings consequently showed a dynamic modulation of mite reproduction and recapping, as well as a direct effect of brood interruption on both traits. To further elucidate the plasticity in the expression of both traits, I studied mite reproduction, recapping behaviour and infestation levels over the course of three years. The resulting extensive dataset unveiled a significant seasonal variation in mite reproduction and recapping. In addition, I show that recapping decreases the reproductive success of mites by increasing delayed developing female offspring and cells lacking male offspring. By establishing a novel picture-based brood investigation method, I could furthermore show that both the removal of brood cells and recapping activity specifically target brood ages in which mite offspring would be expected. Recapping, however, did not cause infertility of mites. Considering the findings of my first study, this points towards complementary mechanisms. This underlines the importance of increased recapping behaviour and decreased mite reproduction as resistance traits, while at the same time emphasising the challenges of reliable data acquisition. To pave the way for a practical application of these findings in breeding, we then investigated the heritability (i.e., the share of genotypic variation on the observed phenotypic variation) of the accounted traits. By elaborating comparable test protocols and compiling data from over 4,000 colonies, we could, for the first time, demonstrate that recapping of infested cells and decreased reproductive success of mites are heritable (and thus selectable) traits in managed honeybee populations. My thesis proves the importance of recapping and decreased mite reproduction as resistance traits and therefore valuable goals for breeding efforts. In this regard, I shed light on the underlying mechanisms of both traits, and present clear evidence for their interaction and heritability.}, subject = {Varroa destructor}, language = {en} } @phdthesis{Gaballa2024, author = {Gaballa, Abdallah Hatem Hassan Hosny Ahmed}, title = {PAF1c drives MYC-mediated immune evasion in pancreatic ductal adenocarcinoma}, doi = {10.25972/OPUS-36045}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-360459}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2024}, abstract = {The expression of the MYC proto-oncogene is elevated in a large proportion of patients with pancreatic ductal adenocarcinoma (PDAC). Previous findings in PDAC have shown that this increased MYC expression mediates immune evasion and promotes S-phase progression. How these functions are mediated and whether a downstream factor of MYC mediates these functions has remained elusive. Recent studies identifying the MYC interactome revealed a complex network of interaction partners, highlighting the need to identify the oncogenic pathway of MYC in an unbiased manner. In this work, we have shown that MYC ensures genomic stability during S-phase and prevents transcription-replication conflicts. Depletion of MYC and inhibition of ATR kinase showed a synergistic effect to induce DNA damage. A targeted siRNA screen targeting downstream factors of MYC revealed that PAF1c is required for DNA repair and S-phase progression. Recruitment of PAF1c to RNAPII was shown to be MYC dependent. PAF1c was shown to be largely dispensable for cell proliferation and regulation of MYC target genes. Depletion of CTR9, a subunit of PAF1c, caused strong tumor regression in a pancreatic ductal adenocarcinoma model, with long-term survival in a subset of mice. This effect was not due to induction of DNA damage, but to restoration of tumor immune surveillance. Depletion of PAF1c resulted in the release of RNAPII with transcription elongation factors, including SPT6, from the bodies of long genes, promoting full-length transcription of short genes. This resulted in the downregulation of long DNA repair genes and the concomitant upregulation of short genes, including MHC class I genes. These data demonstrate that a balance between long and short gene transcription is essential for tumor progression and that interference with PAF1c levels shifts this balance toward a tumor-suppressive transcriptional program. It also directly links MYC-mediated S-phase progression to immune evasion. Unlike MYC, PAF1c has a stable, known folded structure; therefore, the development of a small molecule targeting PAF1c may disrupt the immune evasive function of MYC while sparing its physiological functions in cellular growth.}, subject = {Myc}, language = {en} }