@misc{Heessel2014,
  author    = {Heeßel, Nils P.},
  title     = {Gehlken, Erlend: Weather Omens of Enūma Anu Enlil},
  series = {Orientalistische Literaturzeitung},
  volume    = {109},
  journal   = {Orientalistische Literaturzeitung},
  number    = {6},
  publisher = {De Gruyter Akademie Forschung},
  issn      = {0030-5383},
  doi       = {10.1515/olzg-2014-0138},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-195067},
  pages     = {435-437},
  year      = {2014},
  abstract  = {Rezension zu Gehlken, Erlend: Weather Omens of Enūma Anu Enlil. Thunderstorms, Wind and Rain (Tablets 44-49). Leiden/Boston: Brill 2012. X, 286 S, 47 Pl. 8°= Cuneiform Mo-nographs 43. Hartbd. € 105,00. ISBN 978-90-04-22588-6.},
  language  = {de}
}
@article{LudwigsWeidermann2014,
  author    = {Ludwigs, Markus and Weidermann, Sabine},
  title     = {Drittwirkung der Europ{\"a}ischen Grundfreiheiten - Von der Divergenz zur Konvergenz?},
  series = {JURA - Juristische Ausbildung},
  volume    = {36},
  journal   = {JURA - Juristische Ausbildung},
  number    = {2},
  issn      = {1612-7021},
  doi       = {10.1515/jura-2014-0018},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-195190},
  pages     = {152-165},
  year      = {2014},
  abstract  = {Kein Abstract verf{\"u}gbar.},
  language  = {de}
}
@article{Beck2014,
  author    = {Beck, Lukas},
  title     = {Positive Publizit{\"a}t des Handelsregisters gem. \S 15 Abs. 3 HGB},
  series = {JURA - Juristische Ausbildung},
  volume    = {36},
  journal   = {JURA - Juristische Ausbildung},
  number    = {5},
  issn      = {1612-7021},
  doi       = {10.1515/jura-2014-0059},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-195229},
  pages     = {507-513},
  year      = {2014},
  abstract  = {Kein Abstract verf{\"u}gbar.},
  language  = {de}
}
@misc{Karremann2014,
  author    = {Karremann, Isabel},
  title     = {April London.The Cambridge Introduction to the Eighteenth-Century Novel. Cambridge Introductions to Literature. Cambridge: Cambridge University Press, 2012, 260 pp., \$ 26.99 pb.},
  series = {Anglia},
  volume    = {132},
  journal   = {Anglia},
  number    = {3},
  issn      = {1865-8938},
  doi       = {10.1515/ang-2014-0064},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-195307},
  pages     = {611-615},
  year      = {2014},
  abstract  = {No abstract available.},
  language  = {en}
}
@misc{Gwosdek2014,
  author    = {Gwosdek, Hedwig},
  title     = {Nicholas Orme. English School Exercises, 1420-1530. Studies and Texts 181. Toronto: Pontifical Institute of Mediaeval Studies, 2013, xi + 441 pp., \$ 95.00.},
  series = {Anglia},
  volume    = {132},
  journal   = {Anglia},
  number    = {3},
  issn      = {1865-8938},
  doi       = {10.1515/ang-2014-0063},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-195318},
  pages     = {607-610},
  year      = {2014},
  abstract  = {No abstract available.},
  language  = {en}
}
@misc{Guenther2014,
  author    = {G{\"u}nther, Friederike Felicitas},
  title     = {Dieter Martin/Thomas Seedorf (Hgg.), Lied und Lyrik um 1900},
  series = {Arbitrium},
  volume    = {32},
  journal   = {Arbitrium},
  number    = {1},
  issn      = {0723-2977},
  doi       = {10.1515/arbi-2014-0007},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-195431},
  pages     = {112-115},
  year      = {2014},
  abstract  = {Rezension zu Dieter Martin/Thomas Seedorf (Hgg.), Lied und Lyrik um 1900},
  language  = {de}
}
@article{Kiesler2014,
  author    = {Kiesler, Reinhard},
  title     = {Anja Overbeck / Wolfgang Schweickard / Harald V{\"o}lker (edd.), Lexikon, Variet{\"a}t, Philologie: Romanistische Studien. G{\"u}nter Holtus zum 65. Geburtstag, Berlin, De Gruyter, 2011, XLIV + 824 p.},
  series = {Zeitschrift f{\"u}r romanische Philologie},
  volume    = {130},
  journal   = {Zeitschrift f{\"u}r romanische Philologie},
  number    = {4},
  issn      = {1865-9063},
  doi       = {10.1515/zrp-2014-0108},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-195505},
  pages     = {1165 -- 1170},
  year      = {2014},
  abstract  = {Kein Abstract verf{\"u}gbar.},
  language  = {en}
}
@misc{Kiesler2014,
  author    = {Kiesler, Reinhard},
  title     = {Sabine Bastian / Thierry Bulot / Elisabeth Burr (edd.), Sociolinguistique urbaine. Identit{\´e}s et mise en mots (Sprache - Kultur - Gesellschaft, 6), M{\"u}nchen, Meidenbauer, 2011, 161 p.},
  series = {Zeitschrift f{\"u}r romanische Philologie},
  volume    = {130},
  journal   = {Zeitschrift f{\"u}r romanische Philologie},
  number    = {4},
  issn      = {1865-9063},
  doi       = {10.1515/zrp-2014-0097},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-195517},
  pages     = {1083 -- 1086},
  year      = {2014},
  abstract  = {Kein Abstract verf{\"u}gbar.},
  language  = {de}
}
@article{Kraschl2014,
  author    = {Kraschl, Dominikus},
  title     = {Franz von Kutschera {\"u}ber ungegenst{\"a}ndliche Erfahrungen und ihre (religions-)philosophische Bedeutung},
  series = {Neue Zeitschrift f{\"u}r Systematische Theologie und Religionsphilosophie},
  volume    = {56},
  journal   = {Neue Zeitschrift f{\"u}r Systematische Theologie und Religionsphilosophie},
  number    = {4},
  issn      = {0028-3517},
  doi       = {10.1515/nzsth-2014-0024},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-195533},
  pages     = {422 -- 440},
  year      = {2014},
  abstract  = {Zusammenfassung Der Beitrag diskutiert im Anschluss an Franz von Kutschera die (religions-)philosophische und theologische Bedeutung ungegenst{\"a}ndlicher Erfahrungen. Es handelt sich um Erfahrungen, die sich nicht oder nur bedingt als Erfahrungen eines Subjekts von einem Objekt beschreiben lassen. Besonders in den Blick genommen wird die Relevanz ungegenst{\"a}ndlicher Erfahrungen sowohl f{\"u}r die Semantik religi{\"o}ser Rede als auch f{\"u}r die Epistemologie religi{\"o}ser {\"U}berzeugungen. In diesem Zusammenhang wird argumentiert, dass die kognitive Relevanz dieser Erfahrungen davon abh{\"a}ngt, ob sie innerhalb eines weltanschaulichen Paradigmas einen Beitrag zu einem koh{\"a}renten und umfassenden Verst{\"a}ndnis der uns begegnenden Wirklichkeit leisten.},
  language  = {de}
}
@article{Reber2014,
  author    = {Reber, Elisabeth},
  title     = {Constructing evidence at Prime Minister's Question Time: An analysis of the grammar, semantics and pragmatics of the verb see},
  series = {Intercultural Pragmatics},
  volume    = {11},
  journal   = {Intercultural Pragmatics},
  number    = {3},
  issn      = {1613-365X},
  doi       = {10.1515/ip-2014-0017},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-195549},
  pages     = {357 -- 387},
  year      = {2014},
  abstract  = {Abstract Constructing evidence constitutes a practice to establish the speaker's authority at Prime Minister's Question Time (PMQT), a weekly half-hour session in the British House of Commons. Here the verb see constitutes a resource for both the questioning Leader of the Opposition (LO) and Members of Parliament (MP) as well as for the responding Prime Minister (PM) to claim first-hand perceptual experience. This paper takes an integrated approach, offering a combined analysis of the grammatical formatting, semantics and pragmatics of the verb see in the context of evidential moves at PMQT. It shows how the verb see is functional in referring to the perceptual basis of a claim made and how its grammatical formatting is reflective of the contingencies of the local interactional context. The analysis is grounded in 32 sessions of PMQT (ca. 16 hrs of video-recordings). The results can be summarised as follows: 1) The evidential function of the verb is achieved through its context-specific grammatical formatting and semantics. 2) The reference to the perceptual basis of a claim evoked by see may co-occur with epistemic qualification and evaluative expressions. 3) The formatting of the verb may be indexical of the political relationship between the questioner and the responding PM.},
  language  = {en}
}
@incollection{StaffeldtOtt2014,
  author    = {Staffeldt, Sven and Ott, Christine},
  title     = {Sprechen als kommunikative Ressource. Was die linguistische Pragmatik f{\"u}r den Kompetenzbereich ‚Sprechen' zu bieten hat},
  series = {Deutschunterricht am Gymnasium. Was kann die Sprachwissenschaft leisten?},
  booktitle = {Deutschunterricht am Gymnasium. Was kann die Sprachwissenschaft leisten?},
  publisher = {Schneider Verlag Hohengehren},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-210649},
  publisher      = {Universit{\"a}t W{\"u}rzburg},
  pages     = {66-83},
  year      = {2014},
  abstract  = {Kein Abstract verf{\"u}gbar},
  language  = {de}
}
@incollection{Ott2014,
  author    = {Ott, Christine},
  title     = {Das Schulbuch beim Wort nehmen - Linguistische Methodik in der Schulbuchforschung},
  series = {Methodologie und Methoden der Schulbuch- und Lehrmittelforschung},
  booktitle = {Methodologie und Methoden der Schulbuch- und Lehrmittelforschung},
  publisher = {Verlag Julius Klinkhardt},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-210394},
  publisher      = {Universit{\"a}t W{\"u}rzburg},
  pages     = {254-263},
  year      = {2014},
  abstract  = {Kein Abstract verf{\"u}gbar.},
  language  = {de}
}
@article{PapenfortVogel2014,
  author    = {Papenfort, Kai and Vogel, J{\"o}rg},
  title     = {Small RNA functions in carbon metabolism and virulence of enteric pathogens},
  series = {Frontiers in Cellular and Infection Microbiology},
  volume    = {4},
  journal   = {Frontiers in Cellular and Infection Microbiology},
  number    = {91},
  issn      = {2235-2988},
  doi       = {10.3389/fcimb.2014.00091},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-197520},
  year      = {2014},
  abstract  = {Enteric pathogens often cycle between virulent and saprophytic lifestyles. To endure these frequent changes in nutrient availability and composition bacteria possess an arsenal of regulatory and metabolic genes allowing rapid adaptation and high flexibility. While numerous proteins have been characterized with regard to metabolic control in pathogenic bacteria, small non-coding RNAs have emerged as additional regulators of metabolism. Recent advances in sequencing technology have vastly increased the number of candidate regulatory RNAs and several of them have been found to act at the interface of bacterial metabolism and virulence factor expression. Importantly, studying these riboregulators has not only provided insight into their metabolic control functions but also revealed new mechanisms of post-transcriptional gene control. This review will focus on the recent advances in this area of host-microbe interaction and discuss how regulatory small RNAs may help coordinate metabolism and virulence of enteric pathogens.},
  language  = {en}
}
@book{OPUS4-18074,
  title     = {Das Shopping Center Ph{\"a}nomen - Aktuelle Entwicklungen und Wirkungen},
  editor    = {Kulke, Elmar and Rauh, J{\"u}rgen},
  publisher = {MetaGIS Infosysteme},
  address   = {Mannheim},
  isbn      = {978-3-936438-70-3},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-180744},
  publisher      = {Universit{\"a}t W{\"u}rzburg},
  pages     = {167},
  year      = {2014},
  abstract  = {Das „Ph{\"a}nomen" Shopping Center besch{\"a}ftigt geographische Handelsforscher und Praktiker seit Jahren gleichermaßen. Dies liegt nicht zuletzt an vielf{\"a}ltigen Prozessen der raum-zeitlichen Ausbreitung, welche auf globaler Ebene zunehmende Internationalisierung, auf der regionalen Ebene r{\"u}cken vermehrt mittelgroße und kleinere St{\"a}dte in den Fokus der Projektentwickler und auf lokaler Ebene ist eine Verlagerung des Ansiedlungsgeschehens von Stadtrandlagen zu innerst{\"a}dtischen Zentren zu beobachten. Auf Akteursseite spielen Projektentwickler und Management eine wichtige Rolle, um Shopping Center zu erfolgreichen Investmentprodukten zu machen, w{\"a}hrend die r{\"a}umliche Planung bei der Bewertung von Projektantr{\"a}gen und bei der Einordnung in st{\"a}dtische Ansiedlungsstrategien und Leitbilder zu ber{\"u}cksichtigen hat, dass Shopping Center eine besondere Raumkonfiguration in den Stadtlandschaften darstellen - mit Auswirkungen auf verschiedene Aspekte der wirtschaftlichen Entwicklungen und des sozialen Lebens. Ihre Vertr{\"a}glichkeit mit bestehenden Einzelhandelsstrukturen, ihre Wirkungen auf die Stadtentwicklung sowie auf Kaufkraftstr{\"o}me mit geeigneten Methoden und unter Ber{\"u}cksichtigung aktueller Prozesse zu untersuchen, ist Anliegen der Forschung und Praxis. Diesem Anliegen widmet sich der vorliegende Sammelband, wobei der Großteil der Beitr{\"a}ge auf den Vortr{\"a}gen einer Fachsitzung im Rahmen des Deutschen Geographentages 2013 in Passau basiert.},
  subject      = {Deutschland},
  language  = {de}
}
@article{CullLimaPradoGodinhoFernandesRodriguesetal.2014,
  author    = {Cull, Benjamin and Lima Prado Godinho, Joseane and Fernandes Rodrigues, Juliany Cola and Frank, Benjamin and Schurigt, Uta and Williams, Roderick AM and Coombs, Graham H and Mottram, Jeremy C},
  title     = {Glycosome turnover in Leishmania major is mediated by autophagy},
  series = {Autophagy},
  volume    = {10},
  journal   = {Autophagy},
  number    = {12},
  doi       = {10.4161/auto.36438},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-150277},
  pages     = {2143-2157},
  year      = {2014},
  abstract  = {Autophagy is a central process behind the cellular remodeling that occurs during differentiation of Leishmania, yet the cargo of the protozoan parasite's autophagosome is unknown. We have identified glycosomes, peroxisome-like organelles that uniquely compartmentalize glycolytic and other metabolic enzymes in Leishmania and other kinetoplastid parasitic protozoa, as autophagosome cargo. It has been proposed that the number of glycosomes and their content change during the Leishmania life cycle as a key adaptation to the different environments encountered. Quantification of RFP-SQL-labeled glycosomes showed that promastigotes of L. major possess ~20 glycosomes per cell, whereas amastigotes contain ~10. Glycosome numbers were significantly greater in promastigotes and amastigotes of autophagy-defective L. major Δatg5 mutants, implicating autophagy in glycosome homeostasis and providing a partial explanation for the previously observed growth and virulence defects of these mutants. Use of GFP-ATG8 to label autophagosomes showed glycosomes to be cargo in ~15\% of them; glycosome-containing autophagosomes were trafficked to the lysosome for degradation. The number of autophagosomes increased 10-fold during differentiation, yet the percentage of glycosome-containing autophagosomes remained constant. This indicates that increased turnover of glycosomes was due to an overall increase in autophagy, rather than an upregulation of autophagosomes containing this cargo. Mitophagy of the single mitochondrion was not observed in L. major during normal growth or differentiation; however, mitochondrial remnants resulting from stress-induced fragmentation colocalized with autophagosomes and lysosomes, indicating that autophagy is used to recycle these damaged organelles. These data show that autophagy in Leishmania has a central role not only in maintaining cellular homeostasis and recycling damaged organelles but crucially in the adaptation to environmental change through the turnover of glycosomes.},
  language  = {en}
}
@article{KuhtzSchneiderElHajjetal.2014,
  author    = {Kuhtz, Juliane and Schneider, Eberhard and El Hajj, Nady and Zimmermann, Lena and Fust, Olga and Linek, Bartosz and Seufert, Rudolf and Hahn, Thomas and Schorsch, Martin and Haaf, Thomas},
  title     = {Epigenetic heterogeneity of developmentally important genes in human sperm: Implications for assisted reproduction outcome},
  series = {Epigenetics},
  volume    = {9},
  journal   = {Epigenetics},
  number    = {12},
  doi       = {10.4161/15592294.2014.988063},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-150261},
  pages     = {1648-1658},
  year      = {2014},
  abstract  = {The molecular basis of male infertility is poorly understood, the majority of cases remaining unsolved. The association of aberrant sperm DNA methylation patterns and compromised semen parameters suggests that disturbances in male germline epigenetic reprogramming contribute to this problem. So far there are only few data on the epigenetic heterogeneity of sperm within a given sample and how to select the best sperm for successful infertility treatment. Limiting dilution bisulfite sequencing of small pools of sperm from fertile donors did not reveal significant differences in the occurrence of abnormal methylation imprints between sperm with and without morphological abnormalities. Intracytoplasmic morphologically selected sperm injection was not associated with an improved epigenetic quality, compared to standard intracytoplasmatic sperm injection. Deep bisulfite sequencing (DBS) of 2 imprinted and 2 pluripotency genes in sperm from men attending a fertility center showed that in both samples with normozoospermia and oligoasthenoteratozoospermia (OAT) the vast majority of sperm alleles was normally (de)methylated and the percentage of epimutations (allele methylation errors) was generally low (<1\%). However, DBS allowed one to identify and quantify these rare epimutations with high accuracy. Sperm samples not leading to a pregnancy, in particular in the OAT group, had significantly more epimutations in the paternally methylated GTL2 gene than samples leading to a live birth. All 13 normozoospermic and 13 OAT samples leading to a child had <1\% GTL2 epimutations, whereas one (7\%) of 14 normozoospermic and 7 (50\%) of 14 OAT samples without pregnancy displayed 1-14\% GTL2 epimutations.},
  language  = {en}
}
@article{Fischer2014,
  author    = {Fischer, Doris},
  title     = {The Impact of Changing Incentives in China on International Cooperation in Social Science Research on China},
  series = {Journal of Current Chinese Affairs},
  volume    = {2},
  journal   = {Journal of Current Chinese Affairs},
  number    = {2},
  issn      = {1868-4874},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-120524},
  pages     = {33-46},
  year      = {2014},
  abstract  = {Over the past three decades, China's fast economic development has induced considerable changes in China's university and research institution landscape, research financing and academic career incentives. This paper argues that these changes have affected the motivation and the ways in which Chinese scholars engage in international research cooperation. Most recently it has been observed that strong pressures on scholars and scientists - especially at leading academic institutions - to excel in international publications while simultaneously fulfilling their obligation to generate income for their institutions can lead to a dilemma with regard to international research cooperation: Those institutions and scholars most interesting for foreign scholars to cooperate with may be the ones with the least amount of both incentive and time to enter into serious cooperation. This article invites us to reflect on the implications of these changes in the incentive structure for cooperation in social science research on China.},
  language  = {en}
}
@article{TulodzieckiHerzigGrafe2014,
  author    = {Tulodziecki, Gerhard and Herzig, Bardo and Grafe, Silke},
  title     = {Medienp{\"a}dagogische Forschung als gestaltungsorientierte Bildungsforschung vor dem Hintergrund praxis- und theorierelevanter Forschungsans{\"a}tze in der Erziehungswissenschaft.},
  series = {MedienP{\"a}dagogik, Zeitschrift f{\"u}r Theorie und Praxis der Medienbildung},
  journal   = {MedienP{\"a}dagogik, Zeitschrift f{\"u}r Theorie und Praxis der Medienbildung},
  issn      = {1424-3636},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-120284},
  year      = {2014},
  abstract  = {In der Diskussion um eine gegenstandsad{\"a}quate Forschungsmethodik f{\"u}r die P{\"a}dagogik bzw. Erziehungswissenschaft stellt deren Bedeutung f{\"u}r eine theoriebasierte Verbesserung der Erziehungs- und Bildungspraxis ein wichtiges Thema dar. Da die Medienp{\"a}dagogik als erziehungswissenschaftliche Teildisziplin zu verstehen ist, gelten f{\"u}r die medienp{\"a}dagogische Forschung gleichermassen die Fragen nach ihrem Stellenwert f{\"u}r die Weiterentwicklung medienp{\"a}dagogischer Praxis und f{\"u}r ihre theoretische Fundierung. Vor diesem Hintergrund werden in unserem Beitrag verschiedene erziehungswissenschaftliche Forschungsans{\"a}tze mit medienp{\"a}dagogischen Bez{\"u}gen skizziert, die in besonderer Weise auf eine theoriebasierte Verbesserung der Erziehungs- und Bildungspraxis zielen: die Aktionsforschung, die praxis- und theorieorientierte Entwicklung und Evaluation von Konzepten f{\"u}r p{\"a}dagogisches Handeln, der Design-Based Research-Ansatz sowie das Konzept der entwicklungsorientierten Bildungsforschung. In einer Zusammenschau werden zehn Merkmale entsprechender Forschungsans{\"a}tze aufgezeigt und im Hinblick auf eine gestaltungsorientierte medienp{\"a}dagogische Forschung kommentiert: Gestaltung als Bestandteil des Forschungsprozesses und der Wissensgenerierung, Praxisrelevanz und Praxistauglichkeit, Reflexion von Wertbez{\"u}gen, Theoriefundierung und Theorieentwicklung, empirische Fundierung und Kontrolle, Forschung als zirkul{\"a}rer und iterativer Prozess, Zusammenwirken von Praxis und Wissenschaft, Forschung als Beitrag zur Professionalisierung, Verkn{\"u}pfung unterschiedlicher Forschungsmethoden, Diskussion von G{\"u}tekriterien und Qualit{\"a}tsstandards.},
  language  = {de}
}
@phdthesis{Makgotlho2014,
  author    = {Makgotlho, Phuti Edward},
  title     = {Molecular characterization of the staphylococcal two component system sae and its role in the regulation of the adhesin Eap under SDS stress stimulation},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-149403},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2014},
  abstract  = {The Staphylococcus aureus two component system (TCS) sae governs expression of numerous virulence factors, including Eap (extracellular adherence protein), which in turn among other functions also mediates invasion of host cells. The sae TCS is encoded by the saePQRS operon, with saeS coding for the sensor histidine kinase (SaeS) and saeR encoding the response regulator (SaeR). The saeRS system is preceded by two additional open reading frames (ORFs), saeP and saeQ, which are predicted to encode a lipoprotein (SaeP) and a membrane protein (SaeQ), respectively. Earlier, we have shown that SDS-containing subinhibitory concentrations of biocides (Perform®) and SDS alone activate sae transcription and increase cellular invasiveness in S. aureus strain Newman. The effect is associated with an amino acid exchange in the N-terminus of SaeS (L18P), specific to strain Newman. In this work, the role of whether the two additional genes, saePQ coding for the accessory proteins SaeP and SaeQ, respectively, are involved in SDS-mediated saeRS was investigated. It could demonstrated that the lack of the SaeP protein resulted in an increased saeRS transcription without SDS stress in both SaeSL/P variants, while the SDS effect was less pronounced on sae and eap expression compared to the Newman wildtype, suggesting that the SaeP protein represses the sae system. Also, SDS-mediated inductions of sae and eap transcription along with enhanced invasion were found to be dependent on presence of the SaeSP variant in Newman wildtype. On the other hand, the study also shows that the saePQ region of the sae operon is required for fully functional two-component system saeRS under normal growth conditions, but it is not involved in SDS-mediated activation of the saeS signaling and sae-target class I gene, eap. In the second approach, the study investigates whether SDS-induced sae expression and host cell invasion is common among S. aureus strains not carrying the (L18P) point mutation. To demonstrate this strain Newman, its isogenic saeS mutants, and various S. aureus isolates were analysed for sae, eap expression and cellular invasiveness. Among the strains tested, SDS exposure resulted only in an increase of sae transcription, Eap production and cellular invasiveness in strain Newman wild type and MRSA strain ST239-635/93R, the latter without an increase in Eap. Interestingly, the epidemic community-associated MRSA strain, USA300 LAC showed a biphasic response in sae transcription at different growth stages, which, however, was not accompanied by increased invasiveness. All other clinical isolates investigated displayed a decrease of the parameters tested. While in strain Newman the SDS effect was due to the saeSP allele, this was not the case in strain ST239-635/93R and the biphasic USA300 strains. Also, increased invasiveness of ST239-635/93R was found to be independent of Eap production. Furthermore, to investigate the global effect of SDS on sae target gene expression, strain Newman wild-type and Newman ∆sae were treated with SDS and analyzed for their transcription profiles of sae target genes using microarray assays. We could show that subinhibitory concentrations of SDS upregulate and downregulate gene expression of several signaling pathways involved in biosynthetic, metabolic pathways as well as virulence, host cell adherence, stress reponse and many hypothetical proteins. In summary, the study sheds light on the role of the upstream region saePQ in SDS-mediated saeRS and eap expression during S. aureus SDS stress. Most importantly, the study also shows that subinhibitory SDS concentrations have pronounced strain-dependent effects on sae transcription and subsequent host cell invasion in S. aureus, with the latter likely to be mediated in some strains by other factors than the known invasin Eap and FnBP proteins. Moreover, there seems to exist more than the saeSP-mediated mechanism for SDS-induced sae transcription in clinical S. aureus isolates. These results help to further understand and clarify virulence and pathogenesis mechanisms and their regulation in S. aureus.},
  subject      = {Staphylococcus aureus},
  language  = {en}
}
@phdthesis{Koch2014,
  author    = {Koch, Miriam},
  title     = {Role of Coagulation Factor XII in Atherosclerosis},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-97850},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2014},
  abstract  = {Atherosclerosis is considered a chronic inflammatory disease of the arterial vessel wall which is not only modulated by innate and adaptive immune responses but also by factors of the blood coagulation system. In general hypercoagulability seems to increase the development and progression of experimental atherosclerosis in mice on an atherogenic background. In addition, the great majority of coagulation proteins including coagulation factor XII (FXII) have been detected in early and advanced human atherosclerotic lesions supporting the cross-link between the coagulation system and atherosclerosis. Moreover, FXII has been detected in close proximity to macrophages, foam cells and smooth muscle cells in these lesions and has been demonstrated to be functionally active in human plaques. Although these data indicate that factor XII may play a role in atherogenesis a direct contribution of FXII to atherogenesis has not been addressed experimentally to date. Furthermore, clinical studies examining the function of FXII in vascular disease have yielded conflicting results. Hence, in order to investigate the function of coagulation factor XII in atherosclerosis apolipoprotein E and FXII-deficient (F12\(^{-/-}\) apoE\(^{-/-}\)) mice were employed. Compared to F12\(^{+/+}\)apoE\(^{-/-}\) controls, atherosclerotic lesion formation was reduced in F12\(^{-/-}\)apoE\(^{-/-}\) mice, associated with diminished systemic T-cell activation and Th1-cell polarization after 12 weeks of high fat diet. Moreover, a significant decrease in plasma levels of complement factor C5a was evidenced in F12\(^{-/-}\)apoE\(^{-/-}\) mice. Interestingly, C5a increased the production of interleukin-12 (IL-12) in dendritic cells (DCs) and enhanced their capacity to trigger antigen-specific interferon-gamma (IFNγ) production in OTII CD4\(^+\) T cells in vitro. Importantly, a reduction in frequencies of IL-12 expressing splenic DCs from atherosclerotic F12\(^{-/-}\)apoE\(^{-/-}\) versus F12\(^{+/+}\)apoE\(^{-/-}\) mice was observed in vivo, accompanied by a diminished splenic Il12 transcript expression and significantly reduced IL-12 serum levels. Consequently, these data reveal FXII to play an important role in atherosclerotic lesion formation and to promote DC-induced and systemic IL 12 expression as well as pro-inflammatory T-cell responses likely at least in part via the activation of the complement system.},
  subject      = {Gerinnungsfaktor XII},
  language  = {en}
}