TY - CHAP A1 - Werner, Rudolf A. A1 - Marcus, Charles A1 - Sheikhbahaei, Sara A1 - Higuchi, Takahiro A1 - Solnes, Lilja B. A1 - Rowe, Steven P. A1 - Buck, Andreas K. A1 - Lapa, Constantin A1 - Javadi, Mehrbod S. T1 - The Impact of Ageing on Dopamine Transporter Imaging T2 - Journal of Nuclear Medicine N2 - No abstract available. KW - Parkinson-Krankheit KW - Parkinson KW - Parkinson Disease KW - DaTscan KW - Ioflupane KW - SPECT KW - molecular imaging KW - ageing Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-162213 UR - http://jnm.snmjournals.org/content/59/supplement_1/1646.abstract SN - 0161-5505 N1 - This research was originally published in JNM. Rudolf A. Werner, Charles Marcus, Sara Sheikhbahaei, Takahiro Higuchi, Lilja B. Solnes, Steven P. Rowe, Andreas K. Buck, Constantin Lapa, Mehrbod S. Javadi. The Impact of Ageing on Dopamine Transporter Imaging. J Nucl Med. May 1, 2018; vol. 59 no. supplement 1:1646. © SNMMI. VL - 59 IS - Supplement No 1 SP - 1646 ER - TY - THES A1 - Wedel, Carolin T1 - The impact of DNA sequence and chromatin on transcription in \(Trypanosoma\) \(brucei\) T1 - Der Einfluss der DNA-Sequenz und der Chromatinstruktur auf die Transkription in \(Trypanosoma\) \(brucei\) N2 - For cellular viability, transcription is a fundamental process. Hereby, the DNA plays the most elemental and highly versatile role. It has long been known that promoters contain conserved and often well-defined motifs, which dictate the site of transcription initiation by providing binding sites for regulatory proteins. However, research within the last decade revealed that it is promoters lacking conserved promoter motifs and transcribing constitutively expressed genes that constitute the majority of promoters in eukaryotes. While the process of transcription initiation is well studied, whether defined DNA sequence motifs are required for the transcription of constitutively expressed genes in eukaryotes remains unknown. In the highly divergent protozoan parasite Trypanosoma brucei, most of the proteincoding genes are organized in large polycistronic transcription units. The genes within one polycistronic transcription unit are generally unrelated and transcribed by a common transcription start site for which no RNA polymerase II promoter motifs have been identified so far. Thus, it is assumed that transcription initiation is not regulated but how transcription is initiated in T. brucei is not known. This study aimed to investigate the requirement of DNA sequence motifs and chromatin structures for transcription initiation in an organism lacking transcriptional regulation. To this end, I performed a systematic analysis to investigate the dependence of transcription initiation on the DNA sequence. I was able to identify GT-rich promoter elements required for directional transcription initiation and targeted deposition of the histone variant H2A.Z, a conserved component during transcription initiation. Furthermore, nucleosome positioning data in this work provide evidence that sites of transcription initiation are rather characterized by broad regions of open and more accessible chromatin than narrow nucleosome depleted regions as it is the case in other eukaryotes. These findings highlight the importance of chromatin during transcription initiation. Polycistronic RNA in T. brucei is separated by adding an independently transcribed miniexon during trans-splicing. The data in this work suggest that nucleosome occupancy plays an important role during RNA maturation by slowing down the progressing polymerase and thereby facilitating the choice of the proper splice site during trans-splicing. Overall, this work investigated the role of the DNA sequence during transcription initiation and nucleosome positioning in a highly divergent eukaryote. Furthermore, the findings shed light on the conservation of the requirement of DNA motifs during transcription initiation and the regulatory potential of chromatin during RNA maturation. The findings improve the understanding of gene expression regulation in T. brucei, a eukaryotic parasite lacking transcriptional Regulation. N2 - Die Transkription ist ein entscheidender Prozess in der Zelle und die DNA-Sequenz nimmt hierbei eine elementare Rolle ein. Promotoren beinhalten spezifische und konservierte DNASequenzen und vermitteln den Start der Transkription durch die Rekrutierung spezifischer Proteine. Jedoch haben Forschungen im vergangenen Jahrzehnt gezeigt, dass die Mehrzahl der Promotoren in eukaryotischen Genomen keine konservierten Promotormotive aufweisen und häufig konstitutiv exprimierte Gene transkribieren. Obgleich der Prozess der Transkriptionsinitiation im Allgemeinen gut erforscht ist, konnte bisher nicht nachgewiesen werden, ob ein definiertes DNA-Motiv während der Transkription von konstitutiv exprimierten Genes erforderlich ist. In dem eukaryotischen und einzelligen Parasiten Trypanosoma brucei ist die Mehrzahl der proteinkodierenden Gene in lange polycistronische Transkriptionseinheiten arrangiert. Diese werden von einem gemeinsamen Transkriptionsstart durch die RNA Polymerase II transkribiert, allerdings konnten hier bisher keine Promotormotive identifiziert werden. Aus diesem Grund besteht die Annahme, dass Transkription keiner Regulation unterliegt. Allgemein ist der Prozess der Transkriptionsinitiation in T. brucei bisher nur wenig verstanden. Um den Zusammenhang zwischen DNA-Motiven und konstitutiver Genexpression näher zu untersuchen und Schlussfolgerungen über die DNA-Sequenz-Abhängigkeit der Transkriptionsinitiation zu ziehen, habe ich eine systematische Analyse in T. brucei durchgeführt. Ich konnte GT-reiche Promotorelemente innerhalb dieser Regionen identifizieren, die sowohl eine gerichtete Transkriptionsinitiation, als auch den gezielten Einbau der Histonvariante H2A.Z in Nukleosomen nahe der Transkriptionsstartstelle vermittelt haben. Des Weiteren zeigten Nukleosomenpositionierungsdaten, dass in Trypanosomen die Transkripitonsstartstellen nicht die charakteristische, nukleosomendepletierte Region, wie für andere Organismen beschrieben, sondern eine offene Chromatinstruktur enthalten. Zusätzlich konnte ich zeigen, dass die Chromatinstruktur eine wichtige Rolle während der mRNAProzessierung spielt. In T. brucei wird die polycistronische pre-mRNA durch das Anfügen eines Miniexons während des sogenannten trans-Splicens in individuelle mRNAs aufgetrennt. Die Daten dieser Arbeit belegen, dass die Anreicherung von Nukleosomen eine Verlangsamung der transkribierenden Polymerase bewirken und sie somit die richtige Wahl der Splicestelle gewährleisten. Zusammenfassend wurde in dieser Arbeit die Rolle der DNA Sequenz während der Transkriptionsinitiation und Nukleosomenpositionierung in einem divergenten Eukaryoten untersucht. Die Erkenntnisse bringen mehr Licht in die Konservierung der Notwendigkeit eines DNA-Motivs während der Transkriptionsinitiation und das regulatorische Potential der Chromatinstruktur während der RNA-Reifung. Zudem verbessern sie das Verständnis der Genexpressionsregulation in T. brucei, einem eukaryotischen Parasiten, der ohne transkriptionelle Regulation überlebt. KW - Transkription KW - Chromatin KW - Trypanosoma brucei KW - Genexpression KW - Epigenetik KW - RNA polymerase II KW - splicing KW - nuclesosome positioning Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-173438 ER - TY - JOUR A1 - Kaiser, Mathias A1 - Burek, Malgorzata A1 - Britz, Stefan A1 - Lankamp, Frauke A1 - Ketelhut, Steffi A1 - Kemper, Björn A1 - Förster, Carola A1 - Gorzelanny, Christian A1 - Goycoolea, Francisco M. T1 - The influence of capsaicin on the integrity of microvascular endothelial cell monolayers JF - International Journal of Molecular Sciences N2 - Microvascular endothelial cells are an essential part of many biological barriers, such as the blood–brain barrier (BBB) and the endothelium of the arteries and veins. A reversible opening strategy to increase the permeability of drugs across the BBB could lead to improved therapies due to enhanced drug bioavailability. Vanilloids, such as capsaicin, are known to reversibly open tight junctions of epithelial and endothelial cells. In this study, we used several in vitro assays with the murine endothelial capillary brain cells (line cEND) as a BBB model to characterize the interaction between capsaicin and endothelial tight junctions. KW - tight junctions KW - capsaicin KW - endothelial cells Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-284865 SN - 1422-0067 VL - 20 IS - 1 ER - TY - JOUR A1 - Frantz, Stefan A1 - Falcao-Pires, Ines A1 - Balligand, Jean-Luc A1 - Bauersachs, Johann A1 - Brutsaert, Dirk A1 - Ciccarelli, Michele A1 - Dawson, Dana A1 - de Windt, Leon J. A1 - Giacca, Mauro A1 - Hamdani, Nazha A1 - Hilfiker-Kleiner, Denise A1 - Hirsch, Emilio A1 - Leite-Moreira, Adelino A1 - Mayr, Manuel A1 - Thum, Thomas A1 - Tocchetti, Carlo G. A1 - van der Velden, Jolanda A1 - Varricchi, Gilda A1 - Heymans, Stephane T1 - The innate immune system in chronic cardiomyopathy: a European Society of Cardiology (ESC) scientific statement from the Working Group on Myocardial Function of the ESC JF - European Journal of Heart Failure N2 - Activation of the immune system in heart failure (HF) has been recognized for over 20 years. Initially, experimental studies demonstrated a maladaptive role of the immune system. However, several phase III trials failed to show beneficial effects in HF with therapies directed against an immune activation. Preclinical studies today describe positive and negative effects of immune activation in HF. These different effects depend on timing and aetiology of HF. Therefore, herein we give a detailed review on immune mechanisms and their importance for the development of HF with a special focus on commonalities and differences between different forms of cardiomyopathies. The role of the immune system in ischaemic, hypertensive, diabetic, toxic, viral, genetic, peripartum, and autoimmune cardiomyopathy is discussed in depth. Overall, initial damage to the heart leads to disease specific activation of the immune system whereas in the chronic phase of HF overlapping mechanisms occur in different aetiologies. KW - immune system KW - macrophage KW - T-cell KW - ischaemic cardiomyopathy KW - hypertensive cardiomyopathy KW - diabetic cardiomyopathy KW - toxic cardiomyopathy KW - viral cardiomyopathy KW - genetic cardiomyopathy KW - peripartum cardiomyopathy KW - autoimmune cardiomyopathy Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-229091 VL - 20 ER - TY - THES A1 - Teichert, Max T1 - The interest rate risk of banks: current topics T1 - Das Zinsänderungsrisiko von Banken: Aktuelle Themen N2 - Die vorliegende Dissertation beschäftigt sich mit dem Zinsänderungsrisiko von Banken. Sie bearbeitet Themen mit hoher aktueller Relevanz angesichts gegenwärtiger Entwicklungen in der Geldpolitik, der Volkswirtschaftslehre und der Bankenregulierung. Im ersten Teil werden vier Grundlagen gelegt. Erstens wird die moderne Auffassung des Bankgeschäfts vorgestellt, der nach Banken Geld in Form von Ersparnissen schaffen, wenn sie Kredite gewähren. Mit dieser Auffassung gehört die Übernahme von Zinsänderungsrisiken zum normalen Bankgeschäft. Zweitens wird ein Überblick über die Mikroökonomie des Bankgeschäfts gegeben, in dem der jüngst vollzogene Wechsel zum Paradigma des Risikos dargestellt wird. Unter diesem Paradigma sind Banken wesentlich Risikonehmer auch von Zinsänderungsrisiko. Drittens wird die Geldtheorie der Transmissionskanäle zusammengefasst, wobei der Fokus auf dem zuletzt starke Beachtung findenden Risikoneigungskanal liegt. Dieser Transmissionskanal stellt auch eine Verbindung zwischen der Geldpolitik und der Übernahme von Zinsänderungsrisiko durch Banken her. Viertens werden Ansätze und Spezifika der Behandlung des Zinsänderungsrisikos von Banken in der ökonomischen Forschung zusammengetragen. Das ist das Handwerkszeug für die Erarbeitung neuer Forschungsbeiträge. Im zweiten Teil werden drei Erweiterungen entwickelt. Die erste Erweiterung begegnet dem nahezu vollständigen Fehlen von spezifischen Daten zum Zinsänderungsrisiko von Banken in Deutschland mit einer umfassenden Auswertung allgemeiner, öffentlich verfügbarer Statistiken. Es zeigt sich, dass das Zinsänderungsrisiko von Banken in Deutschland über dem Durchschnitt des Euroraums liegt und einem steigenden Trend folgt, der sich insbesondere aus einer Verschiebung hin zu kurzfristigerer Refinanzierung speist. Von den unterschiedlichen Arten von Banken in Deutschland präsentieren sich Sparkassen und Genossenschaftsbanken als besonders exponiert. Die zweite Erweiterung untersucht die Veränderungen der Zinsstruktur in Deutschland und nimmt damit die zweite Komponente des Zinsänderungsrisikos neben der Position der Banken in den Blick. Analysen historischer sowie prognostizierter Veränderungen weisen auf ein sinkendes Zinsänderungsrisiko hin. Auch auf Basis einer ergänzenden Szenarioanalyse ergeben sich konkrete Kritikpunkte an jüngst auf internationaler Ebene beschlossenen regulatorischen Standards sowie genaue Vorschläge zur Ergänzung im Rahmen ihrer Implementierung. Die dritte Erweiterung adressiert ein mögliches Streben nach Rendite (search for yield) von Banken bei der Übernahme von Zinsänderungsrisiko, die geringere Profitabilität zu höherer Risikoübernahme führen lässt. Ein theoretisches Modell führt dieses Verhalten auf eine plausible Nutzenfunktion von Bankmanagern zurück. Eine empirische Untersuchung belegt die statistische Signifikanz und ökonomische Relevanz mit Daten aus Deutschland. N2 - This book produces three main results. First, from publicly available statistics, it can be inferred that the interest rate risk from on-balance sheet term transformation of banks in Germany exceeds the euro area average and is bound to increase even further. German banks push for shorter-term funding and hardly counteract the increased demand for longer-term loans. Within Germany, savings banks and cooperative banks are particularly engaged. Second, the supervisory interest rate shock scenarios are found to be increasingly detached both from the historic and the forecasted development of interest rates in Germany. In particular, German banks have been exposed to fewer and smaller adverse changes of the term structure. This increasingly limits the informative content of mere exposure measures such as the Basel interest rate coefficient when used as risk measures as is common practice in banking supervision and economic research. An impact assessment further supports the conclusion that the least that is required is a more comprehensive set of shock scenarios. Third and finally, there is a reasonable theoretical rationale and there is strong empirical evidence for banks' search for yield in interest rate risk. In addition to the established positive link between the term spread and the taking of interest rate risk by banks an additional negative link can be explained theoretically and there is significant empirical evidence for its existence and relevance. There is even a threshold of income below which banks' search for yield in interest rate risk surfaces openly. KW - Zinsänderungsrisiko KW - economics KW - banking KW - interest rate risk KW - Bankgeschäft Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-153669 SN - 978-3-95826-070-2 SN - 978-3-95826-071-9 N1 - Parallel erschienen als Druckausgabe in Würzburg University Press, 978-3-95826-070-2, 41,80 EUR. PB - Würzburg University Press CY - Würzburg ET - 1. Auflage ER - TY - JOUR A1 - Gröbner, Susanne N. A1 - Worst, Barbara C. A1 - Weischenfeldt, Joachim A1 - Buchhalter, Ivo A1 - Kleinheinz, Kortine A1 - Rudneva, Vasilisa A. A1 - Johann, Pascal D. A1 - Balasubramanian, Gnana Prakash A1 - Segura-Wang, Maia A1 - Brabetz, Sebastian A1 - Bender, Sebastian A1 - Hutter, Barbara A1 - Sturm, Dominik A1 - Pfaff, Elke A1 - Hübschmann, Daniel A1 - Zipprich, Gideon A1 - Heinold, Michael A1 - Eils, Jürgen A1 - Lawerenz, Christian A1 - Erkek, Serap A1 - Lambo, Sander A1 - Waszak, Sebastian A1 - Blattmann, Claudia A1 - Borkhardt, Arndt A1 - Kuhlen, Michaela A1 - Eggert, Angelika A1 - Fulda, Simone A1 - Gessler, Manfred A1 - Wegert, Jenny A1 - Kappler, Roland A1 - Baumhoer, Daniel A1 - Stefan, Burdach A1 - Kirschner-Schwabe, Renate A1 - Kontny, Udo A1 - Kulozik, Andreas E. A1 - Lohmann, Dietmar A1 - Hettmer, Simone A1 - Eckert, Cornelia A1 - Bielack, Stefan A1 - Nathrath, Michaela A1 - Niemeyer, Charlotte A1 - Richter, Günther H. A1 - Schulte, Johannes A1 - Siebert, Reiner A1 - Westermann, Frank A1 - Molenaar, Jan J. A1 - Vassal, Gilles A1 - Witt, Hendrik A1 - Burkhardt, Birgit A1 - Kratz, Christian P. A1 - Witt, Olaf A1 - van Tilburg, Cornelis M. A1 - Kramm, Christof M. A1 - Fleischhack, Gudrun A1 - Dirksen, Uta A1 - Rutkowski, Stefan A1 - Frühwald, Michael A1 - Hoff, Katja von A1 - Wolf, Stephan A1 - Klingebeil, Thomas A1 - Koscielniak, Ewa A1 - Landgraf, Pablo A1 - Koster, Jan A1 - Resnick, Adam C. A1 - Zhang, Jinghui A1 - Liu, Yanling A1 - Zhou, Xin A1 - Waanders, Angela J. A1 - Zwijnenburg, Danny A. A1 - Raman, Pichai A1 - Brors, Benedikt A1 - Weber, Ursula D. A1 - Northcott, Paul A. A1 - Pajtler, Kristian W. A1 - Kool, Marcel A1 - Piro, Rosario M. A1 - Korbel, Jan O. A1 - Schlesner, Matthias A1 - Eils, Roland A1 - Jones, David T. W. A1 - Lichter, Peter A1 - Chavez, Lukas A1 - Zapatka, Marc A1 - Pfister, Stefan M. T1 - The landscape of genomic alterations across childhood cancers JF - Nature N2 - 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. KW - cancer genomics KW - oncogenesis KW - paediatric cancer KW - predictive markers KW - translational research Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-229579 VL - 555 ER - TY - JOUR A1 - Boehm, Anne A1 - Meininger, Susanne A1 - Tesch, Annemarie A1 - Gbureck, Uwe A1 - Müller, Frank A. T1 - The mechanical properties of biocompatible apatite bone cement reinforced with chemically activated carbon fibers JF - Materials N2 - Calcium phosphate cement (CPC) is a well-established bone replacement material in dentistry and orthopedics. CPC mimics the physicochemical properties of natural bone and therefore shows excellent in vivo behavior. However, due to their brittleness, the application of CPC implants is limited to non-load bearing areas. Generally, the fiber-reinforcement of ceramic materials enhances fracture resistance, but simultaneously reduces the strength of the composite. Combining strong C-fiber reinforcement with a hydroxyapatite to form a CPC with a chemical modification of the fiber surface allowed us to adjust the fiber–matrix interface and consequently the fracture behavior. Thus, we could demonstrate enhanced mechanical properties of CPC in terms of bending strength and work of fracture to a strain of 5% (WOF5). Hereby, the strength increased by a factor of four from 9.2 ± 1.7 to 38.4 ± 1.7 MPa. Simultaneously, the WOF5 increased from 0.02 ± 0.004 to 2.0 ± 0.6 kJ∙m−2, when utilizing an aqua regia/CaCl2 pretreatment. The cell proliferation and activity of MG63 osteoblast-like cells as biocompatibility markers were not affected by fiber addition nor by fiber treatment. CPC reinforced with chemically activated C-fibers is a promising bone replacement material for load-bearing applications. KW - calcium phosphate cement KW - damage tolerant cement KW - carbon fiber reinforcement KW - interface control KW - fiber–matrix interaction Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-197808 SN - 1996-1944 VL - 11 IS - 2 ER - TY - THES A1 - Schücker, Katharina T1 - The molecular architecture of the meiotic chromosome axis as revealed by super-resolution microscopy T1 - Die molekulare Architektur der meiotischen Chromosomenachse dargestellt mit hochauflösender Mikroskopie N2 - During meiosis proteins of the chromosome axis are important for monitoring chromatin structure and condensation, for pairing and segregation of chromosomes, as well as for accurate recombination. They include HORMA-domain proteins, proteins of the DNA repair system, synaptonemal complex (SC) proteins, condensins and cohesins. To understand more about their function in shaping the meiotic chromosome it is crucial to establish a defined model of their molecular architecture. Up to now their molecular organization was analysed using conventional methods, like confocal scanning microscopy (CLSM) and transmission electron microscopy (TEM). Unfortunately, these techniques are limited either by their resolution power or their localization accuracy. In conclusion, a lot of data on the molecular organization of chromosome axis proteins stays elusive. For this thesis the molecular structure of the murine synaptonemal complex (SC) and the localization of its proteins as well as of three cohesins was analysed with isotropic resolution, providing new insights into their architecture and topography on a nanoscale level. This was done using immunofluorescence labelling in combination with super-resolution microscopy, line profiles and average position determination. The results show that the murine SC has a width of 221.6 nm ± 6.1 nm including a central region (CR) of 148.2 nm ± 2.6 nm. In the CR a multi-layered organization of the central element (CE) proteins was verified by measuring their strand diameters and strand distances and additionally by imaging potential anchoring sites of SYCP1 (synaptonemal complex protein 1) to the lateral elements (LEs). We were able to show that the two LEs proteins SYCP2 and SYCP3 do co-localize alongside their axis and that there is no significant preferential localization towards the inner LE axis of SYCP2. The presented results also predict an orderly organization of murine cohesin complexes (CCs) alongside the chromosome axis in germ cells and support the hypothesis that cohesins in the CR of the SC function independent of CCs. In the end new information on the molecular organization of two main components of the murine chromosome axis were retrieved with nanometer precision and previously unknown details of their molecular architecture and topography were unravelled. N2 - Innerhalb der Meiose sind Proteine der Chromosomenachse wichtig für das Monitoring der Chromatinstruktur und dessen Kondensation, sowie für die Paarung und Trennung der Chromosomen und für eine fehlerfreie Rekombination. Zu diesen Proteinen zählen HORMA-domain Proteine, Proteine des DNA-Reparatur-Systems und des synaptonemalen Komplexes, sowie Kohäsine und Kondesine. Um mehr über ihre Rolle in der Formgebung meiotischer Chromosomen zu erfahren, ist es unabdingbar ein genau definiertes Modell über ihre molekulare Architektur zu erstellen. Bis jetzt wurde ihre molekulare Organisation mit konventionellen Methoden wie dem konfokalen Laser-Scanning-Mikroskop (CLSM) und dem Transmissionselektronenmikroskop (TEM) untersucht. Beide Techniken sind jedoch entweder in ihrer Auflösung oder ihrer Lokalisationsgenauigkeit beschränkt, wodurch viele Daten zur molekularen Organisation der Chromosomenachse noch nicht erfasst werden konnten. Die vorliegende Arbeit untersucht mit isotropischer Auflösung die molekulare Struktur des synaptonemalen Komplexes (SC) der Maus und die Lokalisation seiner Proteine, sowie die Lokalisation von drei Kohäsinen, was neue Einsichten in deren Architektur und Topographie auf der nanomolekularen Ebene erbrachte. Dies gelang durch die Verwendung von Immunfluoreszenzmarkierungen in Kombination mit hochauflösender Mikroskopie, Linienprofilen und durchschnittlicher Positionsbestimmung. Es konnte gezeigt werden, dass der murine SC eine Weite von 221,6 nm ± 6,1 nm besitzt, inklusive einer 148,2 nm ± 2,6 nm weiten zentralen Region (CR). Innerhalb der CR konnte eine mehrschichtige Anordnung der Proteine des zentralen Elements (CE) bestätigt werden. Dies gelang indem ihre Strangdurchmesser und –abstände gemessen worden sind und zusätzlich potentielle Bindestellen von SYCP1 (synaptonemal complex protein 1) an den lateral Elementen des SCs (LEs) abgebildet werden konnten. Zusätzlich konnte gezeigt werden, dass die beiden LE Proteine, SYCP2 und SYCP3, kolokalisieren. Dabei zeigte SYCP2 keine präferentielle Lokalisation im inneren Bereich der LE. Die Ergebnisse der vorliegenden Arbeit deuten auf eine organisierte Anordnung der murinen Kohäsin Komplexe (CCs) entlang der Chromosomenachse in Keimzellen hin und unterstützen die Hypothese, dass Kohäsine innerhalb der CR des SC eine Funktion unabhängig der von CCs haben. Schlussendlich konnten neue Informationen zur molekularen Anordnung von zwei wichtigen Komponenten der murinen Chromosomenachse mit einer Präzision im Nanometerbereich gewonnen werden und bisher nicht bekannte Details ihrer molekularen Architektur und Topographie aufgedeckt werden. KW - Meiose KW - Super-resolution microscopy KW - Meiosis KW - Synaptonemal complex KW - Cohesin complex Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-144199 ER - TY - JOUR A1 - Sanyal, Anirban A1 - Wallaschek, Nina A1 - Glass, Mandy A1 - Flamand, Louis A1 - Wight, Darren J. A1 - Kaufer, Benedikt B. T1 - The ND10 Complex Represses Lytic Human Herpesvirus 6A Replication and Promotes Silencing of the Viral Genome JF - Viruses N2 - Human herpesvirus 6A (HHV-6A) replicates in peripheral blood mononuclear cells (PBMCs) and various T-cell lines in vitro. Intriguingly, the virus can also establish latency in these cells, but it remains unknown what influences the decision between lytic replication and the latency of the virus. Incoming virus genomes are confronted with the nuclear domain 10 (ND10) complex as part of an intrinsic antiviral response. Most herpesviruses can efficiently subvert ND10, but its role in HHV-6A infection remains poorly understood. In this study, we investigated if the ND10 complex affects HHV-6A replication and contributes to the silencing of the virus genome during latency. We could demonstrate that ND10 complex was not dissociated upon infection, while the number of ND10 bodies was reduced in lytically infected cells. Virus replication was significantly enhanced upon knock down of the ND10 complex using shRNAs against its major constituents promyelocytic leukemia protein (PML), hDaxx, and Sp100. In addition, we could demonstrate that viral genes are more efficiently silenced in the presence of a functional ND10 complex. Our data thereby provides the first evidence that the cellular ND10 complex plays an important role in suppressing HHV-6A lytic replication and the silencing of the virus genome in latently infected cells. KW - human herpesvirus 6 KW - ND10 complex KW - PML KW - lytic replication KW - latency KW - PML nuclear-bodies KW - gene-expression KW - virus-infection KW - in-vitro KW - DNA Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-227337 VL - 10 IS - 8 ER - TY - JOUR A1 - Kohl, Patrick Laurenz A1 - Rutschmann, Benjamin T1 - The neglected bee trees: European beech forests as a home for feral honey bee colonies JF - PeerJ N2 - It is a common belief that feral honey bee colonies (Apis mellifera L.) were eradicated in Europe through the loss of habitats, domestication by man and spread of pathogens and parasites. Interestingly, no scientific data are available, neither about the past nor the present status of naturally nesting honeybee colonies. We expected near-natural beech (Fagus sylvatica L.) forests to provide enough suitable nest sites to be a home for feral honey bee colonies in Europe. Here, we made a first assessment of their occurrence and density in two German woodland areas based on two methods, the tracing of nest sites based on forager flight routes (beelining technique), and the direct inspection of potential cavity trees. Further, we established experimental swarms at forest edges and decoded dances for nest sites performed by scout bees in order to study how far swarms from beekeeper-managed hives would potentially move into a forest. We found that feral honey bee colonies regularly inhabit tree cavities in near-natural beech forests at densities of at least 0.11-0.14 colonies/km\(^{2}\). Colonies were not confined to the forest edges; they were also living deep inside the forests. We estimated a median distance of 2,600 m from the bee trees to the next apiaries, while scout bees in experimental swarms communicated nest sites in close distances (median: 470 m). We extrapolate that there are several thousand feral honey bee colonies in German woodlands. These have to be taken in account when assessing the role of forest areas in providing pollination services to the surrounding land, and their occurrence has implications for the species' perception among researchers, beekeepers and conservationists. This study provides a starting point for investigating the life-histories and the ecological interactions of honey bees in temperate European forest environments. KW - Apis mellifera KW - beech forests KW - black woodpecker KW - dispersal KW - Fagus sylvatica KW - feral honey bees KW - hollow tree KW - swarming KW - tree cavity KW - wild honey bees Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-176512 VL - 6 IS - e4602 ER -