@phdthesis{Faulhaber2003,
  author    = {Faulhaber, Katja},
  title     = {Untersuchungen der Wechselwirkungen von anellierten Chinoliziniumsalzen mit DNA},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-6791},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2003},
  abstract  = {In der vorliegenden Arbeit wurden anellierte Chinoliziniumsalze synthetisiert und auf ihre Wechselwirkung mit DNA hin untersucht. Hierbei wurde in Abh{\"a}ngigkeit vom Substitutionsmuster sowohl die Bindungsaffinit{\"a}t als auch der Mechanismus, der zur lichtinduzierten DNA-Sch{\"a}digung f{\"u}hrt, aufgekl{\"a}rt.},
  subject      = {Chinolizinderivate},
  language  = {de}
}
@article{HohenauerBerkingSchmidtetal.2013,
  author    = {Hohenauer, Tobias and Berking, Carola and Schmidt, Andreas and Haferkamp, Sebastian and Senft, Daniela and Kammerbauer, Claudia and Fraschka, Sabine and Graf, Saskia Anna and Irmler, Martin and Beckers, Johannes and Flaig, Michael and Aigner, Achim and H{\"o}bel, Sabrina and Hoffmann, Franziska and Hermeking, Heiko and Rothenfusser, Simon and Endres, Stefan and Ruzicka, Thomas and Besch, Robert},
  title     = {The neural crest transcription factor Brn3a is expressed in melanoma and required for cell cycle progression and survival},
  series = {EMBO Molecular Medicine},
  volume    = {5},
  journal   = {EMBO Molecular Medicine},
  issn      = {1757-4676},
  doi       = {10.1002/emmm.201201862},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-122193},
  pages     = {919-934},
  year      = {2013},
  abstract  = {Pigment cells and neuronal cells both are derived from the neural crest. Here, we describe the Pit-Oct-Unc (POU) domain transcription factor Brn3a, normally involved in neuronal development, to be frequently expressed in melanoma, but not in melanocytes and nevi. RNAi-mediated silencing of Brn3a strongly reduced the viability of melanoma cell lines and decreased tumour growth in vivo. In melanoma cell lines, inhibition of Brn3a caused DNA double-strand breaks as evidenced by Mre11/Rad50-containing nuclear foci. Activated DNA damage signalling caused stabilization of the tumour suppressor p53, which resulted in cell cycle arrest and apoptosis. When Brn3a was ectopically expressed in primary melanocytes and fibroblasts, anchorage-independent growth was increased. In tumourigenic melanocytes and fibroblasts, Brn3a accelerated tumour growth in vivo. Furthermore, Brn3a cooperated with proliferation pathways such as oncogenic BRAF, by reducing oncogene-induced senescence in non-malignant melanocytes. Together, these results identify Brn3a as a new factor in melanoma that is essential for melanoma cell survival and that promotes melanocytic transformation and tumourigenesis.},
  language  = {en}
}
@article{SanyalWallaschekGlassetal.2018,
  author    = {Sanyal, Anirban and Wallaschek, Nina and Glass, Mandy and Flamand, Louis and Wight, Darren J. and Kaufer, Benedikt B.},
  title     = {The ND10 Complex Represses Lytic Human Herpesvirus 6A Replication and Promotes Silencing of the Viral Genome},
  series = {Viruses},
  volume    = {10},
  journal   = {Viruses},
  number    = {8},
  doi       = {10.3390/v10080401},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-227337},
  pages     = {401, 1-11},
  year      = {2018},
  abstract  = {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.},
  language  = {en}
}
@article{NeitzBessiKachleretal.2022,
  author    = {Neitz, Hermann and Bessi, Irene and Kachler, Valentin and Michel, Manuela and H{\"o}bartner, Claudia},
  title     = {Tailored tolane-perfluorotolane assembly as supramolecular base pair replacement in DNA},
  series = {Angewandte Chemie International Edition},
  volume    = {62},
  journal   = {Angewandte Chemie International Edition},
  number    = {1},
  doi       = {10.1002/anie.202214456},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-312575},
  year      = {2022},
  abstract  = {Arene-fluoroarene interactions offer outstanding possibilities for engineering of supramolecular systems, including nucleic acids. Here, we implement the tolane-perfluorotolane interaction as base pair replacement in DNA. Tolane (THH) and perfluorotolane (TFF) moieties were connected to acyclic backbone units, comprising glycol nucleic acid (GNA) or butyl nucleic acid (BuNA) building blocks, that were incorporated via phosphoramidite chemistry at opposite positions in a DNA duplex. Thermodynamic analyses by UV thermal melting revealed a compelling stabilization by THH/TFF heteropairs only when connected to the BuNA backbone, but not with the shorter GNA linker. Detailed NMR studies confirmed the preference of the BuNA backbone for enhanced polar π-stacking. This work defines how orthogonal supramolecular interactions can be tailored by small constitutional changes in the DNA backbone, and it inspires future studies of arene-fluoroarene-programmed assembly of DNA.},
  language  = {en}
}
@phdthesis{Gershberg2016,
  author    = {Gershberg, Jana},
  title     = {Self-assembled Perylene Bisimide Dimers and their Interaction with Double-stranded DNA},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-136725},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2016},
  abstract  = {The self-assembly of molecules based on π-π-interactions and hydrogen bonding is of significant importance in nature. These processes enable the formation of complex supramolecular structures with diverse functions. For the transfer of the concepts from nature to artificial supramolecular structures, a basic understanding of those processes is needed. For this purpose, π-conjugated aromatic molecules with an easy synthetic access are suitable as their functionalities can be changed effortless. Perylene bisimide (PBIs) dyes are attractive candidates since they fulfill these requirements owing to their tendency to self-assemble in solution due to their large aromatic π-surfaces. Furthermore, the changes of the optical properties (for instance absorption, emission or circular dichroism) of PBI dyes, caused by their self-assembly, are easy to study experimentally. Structural variations of PBI dyes including additional non-covalent interactions, such as hydro-gen bonding, enable to direct their self-assembly process. Thus, the formation of interesting su-pramolecular structures of PBI dyes could be realized, although, often of undefined size. The aim of this thesis was to develop strategies to restrict the aggregate size of PBI dyes. Therefore, de-fined structural features of PBI molecules were combined and a variation of external influences such as solvent and concentration included. Furthermore, DNA was utilized as a template for the limitation of the aggregate size of PBI dyes. Chapters 1 and 2 provide general information and describe examples from literature which are necessary to understand the following experimental work. The first chapter is based on the inter-actions of various molecules with DNA. Therefore, DNA is considered as a supramolecular biom-acromolecule containing specific structural and functional features to interact with small mole-cules. Afterwards, the main interaction modes of small molecules with DNA such as electrostatic interaction, intercalation and groove binding with corresponding examples are discussed. Among all techniques applied to study the interaction of ligands with DNA, UV/Vis absorption, fluores-cence and circular dichroism spectroscopy were described in detail. At the end of this chapter, examples of already pre-associated systems showing interactions with DNA are presented. The second chapter is focused on the determination and mathematic evaluation of the self-assembly processes. The simplest models such as monomer-dimer and isodesmic model are de-scribed and supplemented by examples. Furthermore, the simplest modification of the isodesmic model, the K2-K model, is presented. Additionally, experimental problems, which may arise dur-ing the investigations of the self-assembly processes, are addressed. For the description of the entire self-assembly process, a sufficiently large concentration range and an appropriate measure-ment method that is sensitive in this concentration range is necessary. Furthermore, the full transi-tion from the monomeric to the aggregated species has to be spectroscopically ascertainable. This enables an accurate mathematic evaluation of the self-assembly process and provides meaningful binding constants. The self-assembly pathway can be controlled by the variation of solvent, con-centration or temperature. However, this pathway can also be directed by a rational design of the molecular structure of the considered system. For example, a specific interplay of π-π-interactions and hydrogen bonding may promote isodesmic as well as cooperative growth into large struc-tures. The main focus of this thesis is to develop strategies to control the aggregate size of PBI dyes (Chapter 3). For this purpose, a PBI scaffold was designed which contains hydrogen bonding amide functions at the imide positions derived from the amino acid L-alanine and solubilizing side groups in the periphery (Figure 81). The variations of the residues R/R' range from didodecylox-yphenyl, didodecylphenyl, dioligo(ethylene glycol)phenyl to branched and linear alkyl chains. The most extensive study of the aggregation behavior was performed for the PBI dye 5. Concen-tration-dependent 1H NMR and UV/Vis absorption measurements clearly revealed the formation of dimers in chloroform. Further investigations by means of 2D NMR, VPO and ITC confirmed the exclusive presence of dimer aggregates of PBI 5 in the investigated concentration range. Mo-lecular modelling studies, supported by NMR and FT-IR experiments, provided structural reasons for the absence of further growth into larger aggregates. The specific combination of π-π interac-tions and hydrogen bonds between the NH groups of the amide groups and the carbonyl oxygen atoms of the PBI core are decisive for the formation of the discrete dimer stack (see Figure 82). The investigations of the aggregation behavior of PBIs 6-9 were less extensive but consistent with the results obtained for PBI 5. However, the determined binding constants vary over a considera-ble range of 1.1 x 102 M-1 (PBI 8) to 1.4 x 104 M-1 (PBI 5). These differences could be attributed to structural variations of the dyes. The electron-rich phenyl substituent promoted the aggregation tendency of PBIs 5-7 compared with 8 and 9 that carry only alkyl side chains. Thus, the π-π in-teractions of bay-unsubstituted PBI cores in combination with hydrogen bonding of the amide functions control the formation of discrete dimers of these PBI dyes. The variation of conditions, such as solvent, change the aggregation behavior of PBI dyes. In the solvents toluene and/or methylcyclohexane, anti-cooperative growth into larger aggregates of PBI 5 was observed (Chapter 4). The important feature of this self-assembly process is the absence of isosbestic points over the whole concentration range in the UV/Vis absorption measurements. The preference for the dimeric species of PBI 5 remained in both solvents as well as in mixtures of them, but upon increasing the concentration these dimers self-assemble into larger aggregates. An important feature of the self-assembly process is the preferred formation of even-numbered aggregates compared to the odd-numbered ones (see Figure 83). Although, the conventional K2-K model provides plausible binding constants, it is not capable to describe the aggregation behavior adequately, since it considers a continuous size distribution. The gradual aggregation process over dimers, tetramers, hexamers, etc. was therefore analyzed with a newly developed K2-K model for anti-cooperative supramolecular polymerization. By the global analysis of the UV/Vis absorption spectra a very good agreement between the experimental and simulated spectra, which were based on the new K2-K model, was obtained. Furthermore, the calculated UV/Vis absorption spectra of a dimer and an aggregate highlighted the most important structural differences. The absorption spectrum of the dimer still has a pronounced vibronic structure which gets lost in the spectrum of the aggregate. In another part of this work, a series of water soluble PBI dyes were described which contain similar PBI scaffolds as PBIs 5-8 (Chapter 5). These PBI dyes self-assemble into similar dimer aggregates in water due to their positively charged side chains causing electrostatic repulsion be-tween the molecules (see Figure 84). Here, however, the self-assembly behavior has not been studied thoroughly in water due to the similarities of already reported PBI dyes. Instead, the focus here is on the characterization of the interactions of these dyes with DNA/RNA. The comprehensive studies using thermal denaturation experiments showed the high stability of these PBI/polynucleotide complexes. The spermine-functionalized PBI dyes having six positive charges showed strong interactions with DNA/RNA which was expressed in a signif-icant increase of the melting temperatures of DNA/RNA (ΔTm values between 7 and > 35 ° C). The dioxa analogues containing only two positive charges had lower enhancement of the melting temperature of DNA/RNA (ΔTm values between 3 and 30 ° C). A similar trend has been observed in the fluorimetric titrations. The spermine-functionalized PBI dyes showed high binding con-stants (log Ks = 9.2 - 9.8), independently of the used polynucleotides. In contrast, the dioxa ana-logues displayed smaller binding constants (log Ks = 6.5 - 7.9) without any correlation between binding affinity and binding strength of the PBI dyes and the applied polynucleotides. The CD-spectroscopic measurements revealed significant differences in the binding properties of the dyes with DNA/RNA. They were dependent on the steric hindrance of the amino acid residues at the imide position and their configuration on one side and the grooves properties of ds-DNA/RNA on the other side. The spectroscopic results confirmed the formation of excitonically coupled PBI dimers in the minor groove of ds-DNA and the major groove of ds-RNA. Depending on the se-quence, the grooves of the polynucleotides provide different amount of space for embedding molecules. The guanine amino groups protrude into the minor groove of the polynucleotide poly(dG-dC)2 increasing the steric hindrance, which is not the case for poly(dA-dT)2. Molecular modeling studies showed that the PBI dimers penetrate deeper into the groove of poly(dA-dT)2 due to the absence of the steric hindrance, in comparison to the groove of poly(dG-dC)2 (see Figure 85).},
  subject      = {Perylentetracarbons{\"a}urederivate},
  language  = {en}
}
@article{CaviezelAeschbachLutzetal.1984,
  author    = {Caviezel, M. and Aeschbach, A. P. and Lutz, Werner K. and Schlatter, C.},
  title     = {Reduction of covalent binding of aflatoxin B1 to rabbit liver DNA after immunization against this carcinogen},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-80116},
  year      = {1984},
  abstract  = {The covalent binding of [3H]aflatoxin B1 (AF) to liver DNA was determined, 6 h after oral administration to male rabbits. A Covalent Binding Index, CBI (flmol AF/mol DNA-P)/(mmol AF/kg b. w.) = 8,500 was found. Pretreatment of rabbits with AF coupled to bovine serum albumin in Freund's adjuvant led to the production of AF-directed antibodies. Administration of [3H]AF to such immunized rabbits resulted in a CJH of only 2,500, i.e., the iiDJ{.lUnization provided a protection by a factor of more than 3. Although this is encouraging evidence for the potential of active immunization against genotoxic carcinogens, a nurober of pointswill have to be clarified, such as the time course for the DNA binding and the question of a possible shift to other target cells.},
  subject      = {Krebs},
  language  = {en}
}
@article{SchrautJakobWeidneretal.2014,
  author    = {Schraut, K. G. and Jakob, S. B. and Weidner, M. T. and Schmitt, A. G. and Scholz, C. J. and Strekalova, T. and El Hajj, N. and Eijssen, L. M. T. and Domschke, K. and Reif, A. and Haaf, T. and Ortega, G. and Steinbusch, H. W. M. and Lesch, K. P. and Van den Hove, D. L.},
  title     = {Prenatal stress-induced programming of genome-wide promoter DNA methylation in 5-HTT-deficient mice},
  series = {Translational Psychiatry},
  volume    = {4},
  journal   = {Translational Psychiatry},
  doi       = {10.1038/tp.2014.107},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-119199},
  pages     = {e473},
  year      = {2014},
  abstract  = {The serotonin transporter gene (5-HTT/SLC6A4)-linked polymorphic region has been suggested to have a modulatory role in mediating effects of early-life stress exposure on psychopathology rendering carriers of the low-expression short (s)-variant more vulnerable to environmental adversity in later life. The underlying molecular mechanisms of this gene-by-environment interaction are not well understood, but epigenetic regulation including differential DNA methylation has been postulated to have a critical role. Recently, we used a maternal restraint stress paradigm of prenatal stress (PS) in 5-HTT-deficient mice and showed that the effects on behavior and gene expression were particularly marked in the hippocampus of female 5-Htt+/- offspring. Here, we examined to which extent these effects are mediated by differential methylation of DNA. For this purpose, we performed a genome-wide hippocampal DNA methylation screening using methylated-DNA immunoprecipitation (MeDIP) on Affymetrix GeneChip Mouse Promoter 1.0 R arrays. Using hippocampal DNA from the same mice as assessed before enabled us to correlate gene-specific DNA methylation, mRNA expression and behavior. We found that 5-Htt genotype, PS and their interaction differentially affected the DNA methylation signature of numerous genes, a subset of which showed overlap with the expression profiles of the corresponding transcripts. For example, a differentially methylated region in the gene encoding myelin basic protein (Mbp) was associated with its expression in a 5-Htt-, PS- and 5-Htt × PS-dependent manner. Subsequent fine-mapping of this Mbp locus linked the methylation status of two specific CpG sites to Mbp expression and anxiety-related behavior. In conclusion, hippocampal DNA methylation patterns and expression profiles of female prenatally stressed 5-Htt+/- mice suggest that distinct molecular mechanisms, some of which are promoter methylation-dependent, contribute to the behavioral effects of the 5-Htt genotype, PS exposure and their interaction.},
  language  = {en}
}
@article{CuiSchlesingerSchoenhalsetal.2016,
  author    = {Cui, Huanhuan and Schlesinger, Jenny and Schoenhals, Sophia and Tonjes, Martje and Dunkel, Ilona and Meierhofer, David and Cano, Elena and Schulz, Kerstin and Berger, Michael F. and Haack, Timm and Abdelilah-Seyfried, Salim and Bulyk, Martha L. and Sauer, Sascha and Sperling, Silke R.},
  title     = {Phosphorylation of the chromatin remodeling factor DPF3a induces cardiac hypertrophy through releasing HEY repressors from DNA},
  series = {Nucleic Acids Research},
  volume    = {44},
  journal   = {Nucleic Acids Research},
  number    = {6},
  doi       = {10.1093/nar/gkv1244},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-166391},
  pages     = {2538-2553},
  year      = {2016},
  abstract  = {DPF3 (BAF45c) is a member of the BAF chromatin remodeling complex. Two isoforms have been described, namely DPF3a and DPF3b. The latter binds to acetylated and methylated lysine residues of histones. Here, we elaborate on the role of DPF3a and describe a novel pathway of cardiac gene transcription leading to pathological cardiac hypertrophy. Upon hypertrophic stimuli, casein kinase 2 phosphorylates DPF3a at serine 348. This initiates the interaction of DPF3a with the transcriptional repressors HEY, followed by the release of HEY from the DNA. Moreover, BRG1 is bound by DPF3a, and is thus recruited to HEY genomic targets upon interaction of the two components. Consequently, the transcription of downstream targets such as NPPA and GATA4 is initiated and pathological cardiac hypertrophy is established. In human, DPF3a is significantly up-regulated in hypertrophic hearts of patients with hypertrophic cardiomyopathy or aortic stenosis. Taken together, we show that activation of DPF3a upon hypertrophic stimuli switches cardiac fetal gene expression from being silenced by HEY to being activated by BRG1. Thus, we present a novel pathway for pathological cardiac hypertrophy, whose inhibition is a long-term therapeutic goal for the treatment of the course of heart failure.},
  language  = {en}
}
@phdthesis{Arnold2001,
  author    = {Arnold, Markus A.},
  title     = {Oxidative DNA-Sch{\"a}digung durch elektronisch angeregte Carbonylverbindungen und daraus gebildete Radikalspezies},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-1182038},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2001},
  abstract  = {Mittels Laserblitz-Photolyse wurden die Triplettlebenszeiten sowie die L{\"o}schraten der Triplettzust{\"a}nde verschiedener Acetophenonderivate durch dG, 8-oxodG, DNA, molekularen Sauerstoff und die Ketone selbst bestimmt. F{\"u}r AP-OAc, AP und BP wurden Triplettlebensdauern von 7-9 µs gemessen, w{\"a}hrend die Triplettzust{\"a}nde von AP-OH und AP-OtBu aufgrund alpha Spaltung deutlich kurzlebiger waren (ca. 1 µs); die alpha Spaltung konnte EPR-spektroskopisch durch Spinabfangexperimente mit DMPO und TEMPO belegt werden. Im Fall von AP-OMe wurde weder dessen Triplettzustand noch die Bildung von Radikalen detektiert, was auf einer schnell ablaufenden Norrish-Typ-II-Spaltung beruht. Aufgrund dieses photochemischen Verhaltens wurden die Ketone (mit Ausnahme von AP-OMe) in zwei Gruppen klassifiziert, n{\"a}mlich die „Gruppe A"-Ketone (keine Radikalbildung) und die „Gruppe B"-Ketone (Radikalbildner). W{\"a}hrend die „Gruppe A"-Ketone gegen{\"u}ber niedrigen Konzentrationen von DNA (62.5 µM) inaktiv waren, verursachten die bei der Bestrahlung der „Gruppe B"-Ketone generierten Peroxylradikale, neben wenigen direkt induzierten Strangbr{\"u}chen, haupts{\"a}chlich die Guaninoxidationsprodukte 8-oxoGua und guanidinfreisetzende Produkte (GRP). Erst wenn die DNA-Konzentration zehnfach erh{\"o}ht wird (625 µM), tritt bei der Photolyse der „Gruppe A"-Ketone auch DNA-Oxidation durch einen Elektronentransfer von der Guaninbase auf das angeregte Keton ein. Ein analoger Konzentrationseffekt wurde auch in der dG-Oxidation beobachtet, bei niedrigen Substratkonzentrationen sind nur die radikalbildenden „Gruppe B"-Ketone aktiv. Die Tatsache, dass in der dG-Oxidation durch die „Gruppe A"-Ketone kein 8-oxodG detektiert wurde, wurde auf dessen effiziente Oxidation durch dG•+-Radikalkationen zur{\"u}ckgef{\"u}hrt. Die „Gruppe B"-Ketone sind in Abwesenheit von O2 gegen{\"u}ber dG und DNA oxidativ inaktiv, da die in der alpha Spaltung generierten kohlenstoffzentrierten Radikale keine Peroxylradikale bilden k{\"o}nnen. Die „Gruppe A"-Ketone sind gegen{\"u}ber DNA in Abwesenheit wie auch in Anwesenheit von Sauerstoff genauso reaktiv, da der Elektronentransfer von DNA zum Keton unabh{\"a}ngig von Sauerstoff ist. Um mechanistische Einblicke in die oxidative DNA-Sch{\"a}digung zu erlangen, wurden photochemische Modellstudien mit dem Nukleosid dG sowie 8-oxodG durchgef{\"u}hrt, wobei zus{\"a}tzlich Spiroiminodihydantoin gebildet wird. Bis vor kurzem wurde die Struktur dieses Oxidationsproduktes als 4-HO-8-oxodG angenommen, dass zuerst in der dG Oxidation mit Singulettsauerstoff (1O2) beobachtet wurde. Weder Spiroiminodihydantoin noch 4 HO-8-oxodG sind als authentische Verbindungen bekannt, so dass eine zweifelsfreie Strukturaufkl{\"a}rung die Bestimmung der Konnektivit{\"a}t der markierten Positionen erforderte. Diese Zuordnung erfolgte mittels eines SELINQUATE-NMR Spektrums, mit dem schl{\"u}ssig die 4 HO-8-oxodG-Struktur ausgeschlossen wurde. Wie alle „Gruppe B"-Ketone sind auch alle „Gruppe A"-Ketone in Abwesenheit von O2 mit Ausnahme von AP-OAc gegen{\"u}ber dG inert. Dies ist ein Beleg daf{\"u}r, dass der Elektronentransferschritt von dG zum Keton in Abwesenheit von Sauerstoff (im Gegensatz zur DNA-Oxidation) reversibel ist und daher keine Oxidation m{\"o}glich ist, wenn die Ketylradikale nicht durch O2 abgefangen werden. Das aus AP-OAc gebildete Ketylradikal besitzt als einziges einen effektiven unimolekularen Deaktivierungsweg, n{\"a}mlich die Acetation-abspaltung, so dass die Reversibilit{\"a}t nicht mehr m{\"o}glich ist.},
  subject      = {DNS-Sch{\"a}digung},
  language  = {de}
}
@phdthesis{Weissenstein2019,
  author    = {Weißenstein, Annike},
  title     = {Optische Chemosensoren aus Naphthalin- und Perylenbisimid-Farbstoffen},
  doi       = {10.25972/OPUS-16199},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-161990},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2019},
  abstract  = {Die Liste der interessanten nachzuweisenden Analyte ist lang. Deswegen besteht ein großer Bedarf zur Entwicklung neuer fluoreszierender und kolorimetrischer Chemosensoren. Ziel der vorliegenden Arbeit war daher die Synthese und Charakterisierung neuer optischer bzw. fluoreszierender und kolorimetrischer Chemosensoren mit dem Fokus auf die beiden Substanzklassen der Naphthalinbisimide und Perylenbisimide. Der erste Arbeitsschwerpunkt befasste sich mit wasserl{\"o}slichen Naphthalinbisimiden und ist in drei Unterkapitel aufgeteilt (Kapitel III - 1.1.-1.3., Abbildung 79). Im ersten Unterkapitel (Kapitel III - 1.1.) wurden die Synthesen und optischen Eigenschaften der am Kern Amino-substituierten NBIs 60a-h, mit Dicarbons{\"a}ureresten in Imid-Position und 61a-h, mit 2-Dimethylaminoethyl-Gruppen, in polaren L{\"o}sungsmitteln beschrieben. Die systematische Anbringung verschiedener Amino-Substituenten mit steigendem elektronenziehendem Charakter der Aminoreste diente der mechanistischen Aufkl{\"a}rung der optischen Eigenschaften. Eine vollst{\"a}ndige Untersuchung der optischen Eigenschaften erfolgte in w{\"a}ssriger Pufferl{\"o}sung bei pH 2.1 sowie in Methanol und Acetonitril. Der Einfluss der Imid-Substituenten auf die optischen Eigenschaften war wie zu erwarten gering. Die verschiedenen Kern-Substituenten verursachten hingegen eine hypsochrome Verschiebung der Absorptions- und Fluoreszenzmaxima mit steigendem elektronenziehendem Charakter der an der Aminogruppe angebrachten Reste. Ein unerwarteter Trend konnte im Fall der Fluoreszenzquantenausbeute beobachtet werden. In den protischen L{\"o}sungsmitteln Wasser und Methanol wurde eine lineare Abh{\"a}ngigkeit gegen{\"u}ber der Hammett-σmeta-Konstante ermittelt. Mit steigendem elektronenziehendem Charakter der Kern-Amino-Substituenten erfuhr die Quantenausbeute einen Anstieg auf bis zu 39\% in Wasser f{\"u}r NBI 60h, 61h und 45\% in Methanol f{\"u}r 60h. Die Tatsache, dass in Acetonitril keine solche Abh{\"a}ngigkeit gegen{\"u}ber der Hammett-Konstante beobachtet werden konnte legte eine intermolekulare Wasserstoffbr{\"u}cken-Bindung im angeregten Zustand als konkurrierenden Prozess zur Fluoreszenz nahe. Dieser Prozess tritt zwischen den L{\"o}sungsmittel-Molek{\"u}len und der Akzeptorgruppe (Carbonyl-Sauerstoff) der NBIs, welcher einen strahlungslosen Relaxationsprozess bzw. Fluoreszenzl{\"o}schung zur Folge hat, auf. Der Einfluss dieses Prozesses l{\"a}sst sich durch die St{\"a}rke des elektronenziehenden Amino-Substituentens steuern. Die NBIs 60a-h zeigten zudem in potentiometrischen Titrationen in Wasser eine pH-Unabh{\"a}ngigkeit der optischen Eigenschaften bez{\"u}glich des Imid-Substituentens. Dies macht die NBIs mit Dicarbons{\"a}ureresten f{\"u}r die Anwendung in biologischen Systemen im neutralen pH-Milieu oder als chemische Sensoren besonders geeignet. Aufgrund dieser interessanten Befunde wurde im zweiten Unterkapitel (Kapitel III - 1.2.) das dihalogenierte NBI 58 hinsichtlich der Sensoreigenschaften gegen{\"u}ber prim{\"a}ren, sekund{\"a}ren und terti{\"a}ren Amin- bzw. Diamindampf sowie zur Frischekontrolle von Fleisch untersucht. Die Absorptions- und Fluoreszenz-spektroskopische Untersuchung des D{\"u}nnschichtfilms von NBI 58 zeigte die erfolgreiche, selektive Detektion von prim{\"a}ren Aminen und Diaminen bzw. biogenen Aminen. Zum einen konnte mit bloßen Auge ein Farbumschlag von gelb nach rot und zum anderen {\"A}nderungen in den Absorptionsspektren wie die Entstehung einer neuen bathochrom verschobenen Bande im D{\"u}nnschichtfilm beobachtet werden. Die Erh{\"o}hung der Fluoreszenz wie auch die NMR-spektroskopische Untersuchung konnte hingegen ausschließlich in L{\"o}sung detektiert werden. Hiermit konnte die kovalente Wechselwirkung der Amin-Molek{\"u}le mit dem NBI 58 nachgewiesen werden. Trotz der erfolgreichen Detektion biogener Amind{\"a}mpfe erwies sich NBI 58 aufgrund der zu geringen Reaktivit{\"a}t als ungeeigneter chemischer Sensor zur Frischekontrolle von Fleisch. Das dritte und letzte Unterkapitel (Kapitel III - 1.3.) dieses Abschnittes bestand in der Synthese monochlor-monoamino-substituierter NBIs am Kern (65a,b und 66) und der Wechselwirkungen dieser Farbstoffe mit DNS/RNS. Die NBIs 65a,b und 66 wiesen in der Imidstellung 3-Trimethylammoniumpropyl auf, um die Wasserl{\"o}slichkeit zu gew{\"a}hrleisten und die elektrostatische Wechselwirkung mit dem negativ geladenen Phosphatr{\"u}ckgrad der DNS/RNS zu bewirken. Am Kern wurden die Aminos{\"a}uren (S)-2,3-Diaminopropions{\"a}ure (L-Dap) (65a) und (S)-2,6-Diaminohexans{\"a}ure (L-Lys) (65b) sowie 2-Trimethylammoniumethylamin (66) eingef{\"u}gt. Die Untersuchungen mit Hilfe von thermischen Denaturierungsstudien zeigten mit allen NBIs eine deutliche Schmelzpunkterh{\"o}hung der DNS/RNS (ΔTm-Werte zwischen 17 und 35 °C), was die Bildung von NBI/Polynukleotid-Komplexen nahelegte. Diese Komplex-Bildung konnte erneut aufgrund enormer Fluoreszenzl{\"o}schung in fluorimetrischen Titrationsstudien best{\"a}tigt werden. Hier wurden Bindungskonstanten zwischen logK = 5.9 und 7.2 M-1 ermittelt, wobei NBI 65a und poly(dG-dC)2 der st{\"a}rksten Bindungsaffinit{\"a}t und NBI 65a und poly(dA-dT)2 der schw{\"a}chste zugeordnet werden konnte. F{\"u}r NBI 66 wurde die zweith{\"o}chste Bindungsaffinit{\"a}t zu Polynukleotid ct-DNS (logK = 7.08 M-1) beobachtet, w{\"a}hrend dieser Farbstoff sowie 65a,b nur geringe Bindungskonstanten mit dem Polynukleotid polyA-polyU zeigten. Mit Hilfe der CD-spektroskopischen Messungen wurde der Bindungsmodus und die Unterschiede in den Bindungseigenschaften der Farbstoffe mit DNS/RNS ermittelt. Der Großteil aller NBI-Verbindungen interkalierte in einer parallelen Anordnung zwischen die Basenpaare der Polynukleotide. F{\"u}r NBI 65a und poly(dG-dC)2 ließ sich jedoch eine perpendikulare Anordnung zu den Basenpaaren beobachten. ITC-Titrationsstudien komplettierten letztendlich die Untersuchungen zwischen NBIs und Polynukleotiden. Neben Interkalation als Bindungsmodus konnte zus{\"a}tzlich aufgrund der relativ hohen Entropiewerte eine Wechselwirkung zwischen den Substituenten am Kern und den Phosphatgruppen in der kleinen Furche festgestellt werden. Zusammengefasst sind die sterischen Hinderungen der Amino-Substituenten und die Furcheneigenschaften von ds-DNS/RNS entscheidend. Der zweite Arbeitsschwerpunkt ist ebenfalls in drei Unterkapitel (Kapitel III - 2.1.-2.3.) aufgeteilt und befasste sich mit der Synthese und den Sensoreigenschaften kernfunktionalisierter Perylenbisimide (Abbildung 80). Im ersten Abschnitt (Kapitel III - 2.1) wurde die Synthese und die optischen Eigenschaften in L{\"o}sung der am Kern einfach und zweifach Kronenether-funktionalisierten PBIs 77a,b und 71a,b untersucht. In Imidstellung waren alle PBIs mit 2-Trimethylammoniumethyl-Resten funktionalisiert, um eine L{\"o}slichkeit in polaren L{\"o}sungsmitteln zu gew{\"a}hrleisten. Die Buchtpositionen wurden jeweils ein- bzw. zweifach mit den Kronenether-Einheiten 2-Hydroxymethyl-15-Krone-5 und 2-Hydroxymethyl-18-Krone-6 substituiert. Die anschließende Untersuchung der optischen Eigenschaften der PBIs zeigten bei einer Konzentration von 10-5 M in Acetonitril den monomeren Zustand und in Wasser die Ausbildung von H-Aggregaten. Die Fluoreszenzquantenausbeuten erfuhren in Acetonitril mit steigender Kronenether-Ringgr{\"o}ße eine Zunahme von 73\% auf 81\% f{\"u}r die PBIs 71a,b und eine vernachl{\"a}ssigbare geringe Zunahme von 49\% auf 51\% f{\"u}r die PBIs 77a,b. Die Abnahme der Quantenausbeute vom zweifach funktionalisierten zum einfach funktionalisierten PBI um ca. 30\% ließ sich durch die st{\"a}rker ausgepr{\"a}gten strahlungslosen Relaxationsprozesse dieses flexibleren Molek{\"u}ls im angeregten Zustand erkl{\"a}ren. Im zweiten Unterkapitel (Kapitel III - 2.2.) wurden die Selbstassemblierungseigenschaften der synthetisierten PBIs 71a,b und 77a,b in Gegenwart verschiedener Metallionen (Na+, K+, Rb+, Mg2+, Ca2+ und Ba2+) untersucht. Hier konnte eine Abh{\"a}ngigkeit von der Gr{\"o}ße des Kronenether-Rezeptors sowie von der Art der Metallionen gezeigt werden. Die Absorptions- und Fluoreszenz-spektroskopischen Studien der zweifach funktionalisierten PBIs 71a und 71b bei einer PBI-Konzentration von c = 10-5 M zeigten ausschließlich f{\"u}r das 15-Krone-5-Derivat 71a und Ba2+ eine erfolgreiche Ausbildung von PBI-Stapeln mit H-artiger exzitonischer Kopplung. Aufgrund dessen erfuhr das Absorptionsmaximum eine stetige Abnahme einhergehend mit einer hypsochromen Verschiebung und die Fluoreszenz eine vollst{\"a}ndige L{\"o}schung. Zudem konnte eine 1:1-St{\"o}chiometrie der PBI-Stapeln ermittelt werden. Die Anpassung der spektroskopischen {\"A}nderungen an die Hill-Gleichung best{\"a}tigte letztendlich die Bildung eines [2+2]-Sandwich- bzw. Dimer-Komplexes in einem positiv kooperativen Bindungsprozess, in dem mittels ITC eine enorme Stabilisierung der Ba2+-Komplexierung aufgrund der π-π-Wechselwirkung zwischen zwei PBI-Molek{\"u}len, beobachtet wurde. Die Durchf{\"u}hrung der Titrationsexperimente bei einer h{\"o}heren PBI-Konzentration (c = 10-4 M) zusammen mit DOSY-Experimenten versicherten auch in diesem Fall die Formation diskreter Dimerkomplexe. Das einfach funktionalisierte PBI 77a zeigte in der Anwesenheit von Ba2+ {\"a}hnliche optische {\"A}nderungen. Die nachfolgenden Untersuchungen bzw. Interpretationen best{\"a}tigten die Bildung eines [1+2]-Dimerkomplexes mit H-artiger exzitonischer Kopplung, welches aufgrund der flexibleren Komplexstruktur keine Stabilisierung der Ba2+-Komplexierung erfuhr. Neben der Metallionen-Komplexierung war PBI 71b auch in der Lage, in einer 1:2-St{\"o}chiometrie aromatische Aminos{\"a}uren und Dipeptide zu erkennen (Kapitel III - 2.3.), da hier sowohl die Ammoniumgruppen der Aminos{\"a}uren und Dipeptide mit den Kronenethereinheiten als auch die aromatischen Einheiten mit dem PBI-Kern wechselwirken k{\"o}nnen. Fluoreszenz-Titrationsexperimente zeigten, dass die Aminos{\"a}uren L-Tryptophan und L-Tyrosin, welche elektronenreiche aromatische Gruppen aufweisen, und Dipeptide, die diese Aminos{\"a}uren enthalten, die Fluoreszenz des PBIs stark l{\"o}schen. Die Bindungskonstanten der Wirt-Gast-Komplexierung in Acetonitril konnten aufgrund eines statischen L{\"o}schungsprozesses aus den Fluoreszenztitrationsdaten bestimmt werden. Hier wurde beobachtet, dass die Bindungsst{\"a}rke von der Gr{\"o}ße und der elektronischen Natur der aromatischen Einheiten sowie von dem Abstand zwischen der Ammoniumgruppe und der aromatischen Einheit in Aminos{\"a}uren und Dipeptiden abh{\"a}ngt. Die st{\"a}rkste Bindung konnte zwischen Ala-Trp und PBI 71b mit einem Wert von 3.1 x 105 M-1 beobachtet werden. NMR-Studien best{\"a}tigten ebenfalls die Wirt-Gast-Komplexierung, ließen jedoch offen, ob es zu der Bildung von zwei Diastereomeren aufgrund der eingeschr{\"a}nkten Umwandlung der Atrop-Enantiomere (P und M) des PBI 71b kommt oder zu der Bildung von vier Diastereomeren infolge des Chiralit{\"a}tszentrums im Kronenether. Zusammenfassend wurden in dieser Arbeit Naphthalinbisimde und Perylenbisimide hinsichtlich ihrer Eignung als optische Chemosensoren untersucht. Die NBI-Derivate agierten aufgrund ihrer interessanten optischen Eigenschaften als chemische Sensoren selektiv f{\"u}r prim{\"a}ren Amindampf und f{\"u}r die DNS/RNS-Wechselwirkung. Im Fall der PBI-Verbindungen wurden hervorragende fluorometrische Chemosensoren ermittelt, die Ba2+-Ionen und elektronenreiche aromatische Aminos{\"a}uren und Dipeptide in einer deutlichen Fluoreszenzl{\"o}schung detektieren k{\"o}nnen.},
  subject      = {Chemischer Sensor},
  language  = {de}
}
@phdthesis{Siewert2021,
  author    = {Siewert, Aaron},
  title     = {Nucleotide analogs as rigid spin labels for DNA and RNA},
  doi       = {10.25972/OPUS-24765},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-247657},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2021},
  abstract  = {Nucleic acids are one of the important classes of biomolecules together with carbohydrates, proteins and lipids. Both deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) are most well known for their respective roles in the storage and expression of genetic information. Over the course of the last decades, nucleic acids with a variety of other functions have been discovered in biological organisms or created artificially. Examples of these functional nucleic acids are riboswitches, aptamers and ribozymes. In order to gain information regarding their function, several analytical methods can be used. Electron paramagnetic resonance (EPR) spectroscopy is one of several techniques which can be used to study nucleic acid structure and dynamics. However, EPR spectroscopy requires unpaired electrons and because nucleic acids themselves are not paramagnetic, the incorporation of spin labels which carry a radical is necessary. Here, three new spin labels for the analysis of nucleic acids by EPR spectroscopy are presented. All of them share two important design features. First, the paramagnetic center is located at a nitroxide, flanked by ethyl groups to prevent nitroxide degradation, for example during solid phase synthesis. Furthermore, they were designed with rigidity as an important quality, in order to be useful for applications like pulsed electron double resonance (PELDOR) spectroscopy, where independent motion of the spin labels relative to the macromolecule has a noticeable negative effect on the precision of the measurements. Benzi-spin is a spin label which differs from most previous examples of rigid spin labels in that rather than being based on a canonical nucleoside, with a specific base pairing partner, it is supposed to be a universal nucleoside which is sufficiently rigid for EPR measurements when placed opposite to a number of different nucleosides. Benzi-spin was successfully incorporated into a 20 nt oligonucleotide and its base pairing behavior with seven different nucleosides was examined by UV/VIS thermal denaturation and continuous wave (CW) EPR experiments. The results show only minor differences between the different nucleosides, thus confirming the ability of benzi-spin to act as a universally applicable spin label. Lumi-spin is derived from lumichrome. It features a rigid scaffold, as well as a free 2'-hydroxy group, which should make it well suited for PELDOR experiments once it is incorporated into RNA oligonucleotides. E{\c{C}}r is based on the {\c{C}} family of spin labels, which contains the most well known rigid spin labels for nucleic acids to this day. It is essentially a version of E{\c{C}}m with a free 2'-hydroxy group. It was converted to triphosphate E{\c{C}}rTP and used for primer extension experiments to test the viability of enzymatic incorporation of rigid spin labels into oligonucleotides as an alternative to solid-phase synthesis. Incorporation into DNA by Therminator III DNA polymerase in both single-nucleotide and full-length primer extensions was achieved. All three of these spin labels represent further additions to the expanding toolbox of EPR spectroscopy on nucleic acids and might prove valuable for future research.},
  subject      = {Nucleins{\"a}uren},
  language  = {en}
}
@article{HegiUlrichSagelsdorffetal.1990,
  author    = {Hegi, M. E. and Ulrich, D. and Sagelsdorff, P. and Richter, C. and Lutz, Werner K.},
  title     = {No measurable increase in thymidine glycol or 8-hydroxydeoxyguanosine in liver DNA of rats treated with nafenopin or choline-devoid low-methionine diet},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-60790},
  year      = {1990},
  abstract  = {Male rats were treated for 2 months with 1000 ppm nafenopin in the diet or for 4 or 7 days with a choline-devoid low-methionine diet. DNA was isolated from the livers and analyzed for the presence of cis-thymidine glycol-3'-phosphate (cis-dTGp) by 32P-postlabeling and for the Ievel of 8-hydroxy-deoxyguanosine (8-0H-dG) by electrochemical detection (ECD). In no DNA sample was the Ievel of cis-dTGp above the Iimit of detection of 1 modified thymidine per 106 nucleotides. With 8-0H-dG, a background Ievel of this modification of 20 8-0H-dG per 106 nucleosides was found in liver DNA of control rats, which was not affected by either treatment. It is postulated for thymidine glycol that a potential increase was below the Iimit of detection or was rapidly repaired in vivo and that the steady-state Ievel of endogenous 8-hydroxydeoxyguanosine appears not tobe influenced by the treatments chosen.},
  subject      = {Toxikologie},
  language  = {en}
}
@article{AydinliLiangDandekar2022,
  author    = {Aydinli, Muharrem and Liang, Chunguang and Dandekar, Thomas},
  title     = {Motif and conserved module analysis in DNA (promoters, enhancers) and RNA (lncRNA, mRNA) using AlModules},
  series = {Scientific Reports},
  volume    = {12},
  journal   = {Scientific Reports},
  number    = {1},
  doi       = {10.1038/s41598-022-21732-0},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-301268},
  year      = {2022},
  abstract  = {Nucleic acid motifs consist of conserved and variable nucleotide regions. For functional action, several motifs are combined to modules. The tool AIModules allows identification of such motifs including combinations of them and conservation in several nucleic acid stretches. AIModules recognizes conserved motifs and combinations of motifs (modules) allowing a number of interesting biological applications such as analysis of promoter and transcription factor binding sites (TFBS), identification of conserved modules shared between several gene families, e.g. promoter regions, but also analysis of shared and conserved other DNA motifs such as enhancers and silencers, in mRNA (motifs or regulatory elements e.g. for polyadenylation) and lncRNAs. The tool AIModules presented here is an integrated solution for motif analysis, offered as a Web service as well as downloadable software. Several nucleotide sequences are queried for TFBSs using predefined matrices from the JASPAR DB or by using one's own matrices for diverse types of DNA or RNA motif discovery. Furthermore, AIModules can find TFBSs common to two or more sequences. Demanding high or low conservation, AIModules outperforms other solutions in speed and finds more modules (specific combinations of TFBS) than alternative available software. The application also searches RNA motifs such as polyadenylation site or RNA-protein binding motifs as well as DNA motifs such as enhancers as well as user-specified motif combinations (https://bioinfo-wuerz.de/aimodules/; alternative entry pages: https://aimodules.heinzelab.de or https://www.biozentrum.uni-wuerzburg.de/bioinfo/computing/aimodules). The application is free and open source whether used online, on-site, or locally.},
  language  = {en}
}
@phdthesis{Singer2005,
  author    = {Singer, Christian J.},
  title     = {Molekulare Identifizierung von Neisseriaceae und Moraxellaceae mittels ribosomaler DNA-Sequenzierung},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-16823},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2005},
  abstract  = {Die schnelle und verl{\"a}ssliche Identifizierung mikrobiologischer Isolate ist ein fundamentales Ziel der klinischen Mikrobiologie. Bei einigen gram-negativen Spezies ist die klassische ph{\"a}notypische Identifizierung, basierend auf metabolischen, enzymatischen oder serologischen Methoden erschwert, zeitraubend oder nicht suffizient. Durch die Sequenzierung partieller Abschnitte der 16S- oder 23S-rDNA k{\"o}nnen Bakterien meist exakt spezifiziert werden. Hauptziel der vorliegenden Arbeit war es, hypervariable rDNA Abschnitte zu finden, die von stark konservierten Regionen flankiert werden, um auf molekularer Ebene Mitglieder der Familie Neisseriaceae und Moraxellaceae zu diskriminieren. Die inter- und intragenetischen Beziehungen von insgesamt 94 St{\"a}mmen wurden untersucht. Im Vergleich zu den Referenzst{\"a}mmen der Genera waren bei der partiellen 16S-rDNA (E. coli Position 54 - 510) je Spezies durchschnittlich 30 polymorphe Positionen vorhanden. Die partiellen 23S-rDNA Abschnitte (E. coli Position 1400 - 1600) zeigten durchschnittlich 11 polymorphe Positionen. Neisseria macacae und N. mucosa subsp. mucosa (ATCC 19696) zeigten identische 16S- und 23S-rDNA Sequenzen. Die Gruppierung verschiedener Isolate war bei Acinetobacter lwoffii, Moraxella lacunata und Neisseria mucosa an beiden untersuchten Genabschnitten heterogen. Im Fall von N. meningitidis konnte mit Hilfe der 23S-rDNA Daten nicht suffizient gruppiert werden. Die Ergebnisse zeigen eine {\"U}berlegenheit der untersuchten partiellen 16S-rDNA zur Diagnostik der Neisseriaceae und Moraxellaceae. Eine Referenzdatenbank zur Diagnostik von Mikroorganismen sollte mehr als ein Isolat einer Spezies enthalten und zudem einen polyphasischen Ansatz verfolgen. Die Sequenz-Chromatogramme und weitere diagnostisch relevante Informationen wurden mit der „offline"-Datenbank RIDOM_Tool gesammelt und sind ein Teil des Internet-basierenden Service von RIDOM (www.ridom-rdna.de). Eine eingegebene Sequenzfolge kann online eingef{\"u}gt und damit ein direkter Vergleich mit den in der RIDOM Referenzdatenbank existierenden Datens{\"a}tzen initiiert werden.},
  language  = {de}
}
@inproceedings{VivianiLutz1979,
  author    = {Viviani, A. and Lutz, Werner K.},
  title     = {Modulation of the in vivo covalent binding of the carcinogen benzo(a)pyrene to rat liver DNA by selective induction of microsomal and nuclear aryl hydrocarbon hydroxylase activity},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-80132},
  year      = {1979},
  abstract  = {The influence of microsomal (mAHH) and nuclear (nAHH) aryl hydrocarbon hydroxylase activity on the covalent binding of t:titiated benzo(a)pyrene to rat liver DNA was evaluated in vivo. Induction ofmAHH was obtained after phenobarbitone treatment (180\% of control), which increased DNA binding to 210\%, but left the nAHH unchanged. mAHH and nAHH were slightly indilced with dieldrin (130\% and 120\%), but the binding remairred unchanged. The increasing effect of mAHlt as weil as the possibly decreasing effect of nAHH induction on the binding became obvious when the data of 11 individual rats were used to solve the equation Binding = aX(mAHH) + bX(nAHH) + c. Multiple linear regression analysis resulted in positive values for a and c, a negative value for b, and a multiple correlation coefficient R = 0.82. An influence of other enzymes involved in the metabolism of benzo(a)pyrene cannot be excluded. The Study shows clearly that the binding of a foreign compound to DNA in vivo is not only dependent on microsomal enzyme activities but also on nuclear activities even if the latter are considerably lower than those of mic'rosomes.},
  subject      = {DNA},
  language  = {en}
}
@article{ZieglerRichterMahretal.2016,
  author    = {Ziegler, C. and Richter, J. and Mahr, M. and Gajewska, A. and Schiele, M.A. and Gehrmann, A. and Schmidt, B. and Lesch, K.-P. and Lang, T. and Helbig-Lang, S. and Pauli, P. and Kircher, T. and Reif, A. and Rief, W. and Vossbeck-Elsebusch, A.N. and Arolt, V. and Wittchen, H.-U. and Hamm, A.O. and Deckert, J. and Domschke, K.},
  title     = {MAOA gene hypomethylation in panic disorder-reversibility of an epigenetic risk pattern by psychotherapy},
  series = {Translational Psychiatry},
  journal   = {Translational Psychiatry},
  number    = {6},
  doi       = {10.1038/tp.2016.41},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164422},
  pages     = {e773},
  year      = {2016},
  abstract  = {Epigenetic signatures such as methylation of the monoamine oxidase A (MAOA) gene have been found to be altered in panic disorder (PD). Hypothesizing temporal plasticity of epigenetic processes as a mechanism of successful fear extinction, the present psychotherapy-epigenetic study for we believe the first time investigated MAOA methylation changes during the course of exposure-based cognitive behavioral therapy (CBT) in PD. MAOA methylation was compared between N=28 female Caucasian PD patients (discovery sample) and N=28 age- and sex-matched healthy controls via direct sequencing of sodium bisulfite-treated DNA extracted from blood cells. MAOA methylation was furthermore analyzed at baseline (T0) and after a 6-week CBT (T1) in the discovery sample parallelized by a waiting time in healthy controls, as well as in an independent sample of female PD patients (N=20). Patients exhibited lower MAOA methylation than healthy controls (P<0.001), and baseline PD severity correlated negatively with MAOA methylation (P=0.01). In the discovery sample, MAOA methylation increased up to the level of healthy controls along with CBT response (number of panic attacks; T0-T1: +3.37±2.17\%), while non-responders further decreased in methylation (-2.00±1.28\%; P=0.001). In the replication sample, increases in MAOA methylation correlated with agoraphobic symptom reduction after CBT (P=0.02-0.03). The present results support previous evidence for MAOA hypomethylation as a PD risk marker and suggest reversibility of MAOA hypomethylation as a potential epigenetic correlate of response to CBT. The emerging notion of epigenetic signatures as a mechanism of action of psychotherapeutic interventions may promote epigenetic patterns as biomarkers of lasting extinction effects.},
  language  = {en}
}
@article{ThiryScheerGoessens1988,
  author    = {Thiry, Marc and Scheer, Ulrich and Goessens, Guy},
  title     = {Localization of DNA within Ehrlich tumour cells nucleoli by immunoelectron microscopy},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-39327},
  year      = {1988},
  abstract  = {The distribution of DNA in Ehrlich tumour cell nucleoli was investigated by means of an immunocytochemical approach , involving a monoclonal antibody directed against double- and single-stranded DNA. Immunolabelling was performed . either before or after the embedding process. The postembedding labelling method allows better ultrastructural preservation than the preembedding labelling method. In particular, the various nucleolar components are well preserved and identifiable. In the nucleolus, labelling is particularly concentrated over the perinucleolar chromatin and over its intranucleolar invaginations, which penetrate the nucleolar body and often terminate at the fibrillar centres. In addition, aggregates of gold particles are found in the fibrillar centres, preferentially towards the peripheral regions. By contrast, the dense fibrillar component is completely devoid of labelling. The results seem to indicate that DNA containing the rDNA genes is located in the fibrillar centres, with a preference for the peripheral regions. This finding suggests that transcription of the rDNA genes should occur within the confines of the fibrillar centre, probably close to the boundary region of the surrounding dense fibrillar component. The results are discussed in the light of present knowledge of the functional organization of the nucleolus.},
  language  = {en}
}
@phdthesis{Hoeflein2023,
  author    = {H{\"o}flein, Felix},
  title     = {Kinetik der Schistosomen-spezifischen DNA nach Behandlung mit Praziquantel und Bestimmung der Schistosomiasis-Pr{\"a}valenz einer in einem Nicht-Endemiegebiet lebenden Risikopopulation sowie der Evaluation ausgew{\"a}hlter diagnostischer Verfahren},
  doi       = {10.25972/OPUS-29790},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-297909},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2023},
  abstract  = {In dieser Arbeit wurden Bewohner/-innen der W{\"u}rzburger Gemeinschaftsunterk{\"u}nfte f{\"u}r Gefl{\"u}chtete auf das Vorliegen einer Schistosomiasis gescreent. Lag eine behandlungsd{\"u}rftige Infektion vor, wurden die Teilnehmenden mit Praziquantel behandelt, um im nachfolgenden Verlauf freiwillig an der Erstellung einer Schistosomen-DNA-Kinetik mitzuwirken. Eine Besonderheit der Studie lag dabei in der fehlenden M{\"o}glichkeit einer Reinfektion, da sich die Betroffenen w{\"a}hrend des Follow-ups in einem Endemie-freien Gebiet aufhielten. F{\"u}r das Screening kamen ein CCA-Urin-Schnelltest sowie ein ICT zum Einsatz. Die Diagnosesicherung wurde durch die Mikroskopie oder die qPCR angestrebt. Es zeigte sich, dass die Kombination von CCA-Test und ICT einen positiven pr{\"a}diktiven Wert von 80 \% f{\"u}r das tats{\"a}chliche Vorliegen einer Schistosomen-Infektion liefert. Die Schistosomiasis-Pr{\"a}valenz der hier untersuchten, in einem Nicht-Endemiegebiet lebenden Risikopopulation, wurde auf 3,9 \% bestimmt und ist im Vergleich zu bisherigen Ver{\"o}ffentlichungen als niedrig anzusehen. Dabei ist zu beachten, dass die Pr{\"a}valenz zum Teil deutlich {\"u}bersch{\"a}tzt werden kann, sofern der CCA-Urin-Schnelltest als alleiniges Diagnosekriterium eingesetzt wird (Pr{\"a}valenzCCA = 27,6 \%). Die Erstellung der DNA-Kinetik mittels qPCR zeigte, dass die Behandlung mit Praziquantel einen nach 3 Tagen messbaren, signifikanten (p < 0,05) Anstieg der DNA-Konzentration im Serum zur Folge hatte, welcher im weiteren Verlauf kontinuierlich abfiel. Im Mittel wurde nach 48 Tagen der Schwellenwert der DNA-Konzentration unterschritten, der ohne vorausgegangene Behandlung als positiv und therapiebed{\"u}rftig gewertet worden w{\"a}re. Durch Inter- und Extrapolation der gewonnen Daten, konnte eine Funktion errechnet werden, die den zeitlichen Verlauf des Zerfalls der Schistosomen-DNA beschreibt und somit zur Ermittlung weiterer Therapie- und Kontrollm{\"o}glichkeit der Schistosomiasis beitragen kann.},
  subject      = {Schistosomiasis},
  language  = {de}
}
@article{BuchheimKellerKoetschanetal.2011,
  author    = {Buchheim, Mark A. and Keller, Alexander and Koetschan, Christian and F{\"o}rster, Frank and Merget, Benjamin and Wolf, Matthias},
  title     = {Internal Transcribed Spacer 2 (nu ITS2 rRNA) Sequence-Structure Phylogenetics: Towards an Automated Reconstruction of the Green Algal Tree of Life},
  series = {PLoS ONE},
  volume    = {6},
  journal   = {PLoS ONE},
  number    = {2},
  doi       = {10.1371/journal.pone.0016931},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-140866},
  pages     = {e16931},
  year      = {2011},
  abstract  = {Background: Chloroplast-encoded genes (matK and rbcL) have been formally proposed for use in DNA barcoding efforts targeting embryophytes. Extending such a protocol to chlorophytan green algae, though, is fraught with problems including non homology (matK) and heterogeneity that prevents the creation of a universal PCR toolkit (rbcL). Some have advocated the use of the nuclear-encoded, internal transcribed spacer two (ITS2) as an alternative to the traditional chloroplast markers. However, the ITS2 is broadly perceived to be insufficiently conserved or to be confounded by introgression or biparental inheritance patterns, precluding its broad use in phylogenetic reconstruction or as a DNA barcode. A growing body of evidence has shown that simultaneous analysis of nucleotide data with secondary structure information can overcome at least some of the limitations of ITS2. The goal of this investigation was to assess the feasibility of an automated, sequence-structure approach for analysis of IT2 data from a large sampling of phylum Chlorophyta. Methodology/Principal Findings: Sequences and secondary structures from 591 chlorophycean, 741 trebouxiophycean and 938 ulvophycean algae, all obtained from the ITS2 Database, were aligned using a sequence structure-specific scoring matrix. Phylogenetic relationships were reconstructed by Profile Neighbor-Joining coupled with a sequence structure-specific, general time reversible substitution model. Results from analyses of the ITS2 data were robust at multiple nodes and showed considerable congruence with results from published phylogenetic analyses. Conclusions/Significance: Our observations on the power of automated, sequence-structure analyses of ITS2 to reconstruct phylum-level phylogenies of the green algae validate this approach to assessing diversity for large sets of chlorophytan taxa. Moreover, our results indicate that objections to the use of ITS2 for DNA barcoding should be weighed against the utility of an automated, data analysis approach with demonstrated power to reconstruct evolutionary patterns for highly divergent lineages.},
  language  = {en}
}
@article{LutzSchlatter1979,
  author    = {Lutz, Werner K. and Schlatter, C.},
  title     = {In vivo covalent binding of chemicals to DNA as a short-term test for carcinogenicity},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-80127},
  year      = {1979},
  abstract  = {The determination of a covalent binding of radioactive chemieals to DNA in intact mammalian organisms is proposedas a short-term test for carcinogenicity. The effectiveness of covalent binding to rat liver DNA correlates well with the hepatocarcinogenicity known from long-term bioassays. The binding indices range over more than five orders of rriagnitude between the strongest hepatocarcinogen aflatoxin B 1 and the limit of detection of a binding with 100 f-LCi 14C-labelled chemical. The order of magnitude of binding is therefore a surprisingly good quantitative measure for carcinogenicity. The pattern of DNA binding sites is important especially for small alkylating agents where the determination of total binding might indicate a higher carcinogenic potency than is actually observed.},
  subject      = {DNA},
  language  = {de}
}