@article{UeceylerKahnKrameretal.2013,
  author    = {{\"U}{\c{c}}eyler, Nurcan and Kahn, Ann-Kathrin and Kramer, Daniela and Zeller, Daniel and Casanova-Molla, Jordi and Wanner, Christoph and Weidemann, Frank and Katsarava, Zaza and Sommer, Claudia},
  title     = {Impaired small fiber conduction in patients with Fabry disease: a neurophysiological case-control study},
  series = {BMC Neurology},
  journal   = {BMC Neurology},
  doi       = {10.1186/1471-2377-13-47},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-96527},
  year      = {2013},
  abstract  = {Background Fabry disease is an inborn lysosomal storage disorder which is associated with small fiber neuropathy. We set out to investigate small fiber conduction in Fabry patients using pain-related evoked potentials (PREP). Methods In this case-control study we prospectively studied 76 consecutive Fabry patients for electrical small fiber conduction in correlation with small fiber function and morphology. Data were compared with healthy controls using non-parametric statistical tests. All patients underwent neurological examination and were investigated with pain and depression questionnaires. Small fiber function (quantitative sensory testing, QST), morphology (skin punch biopsy), and electrical conduction (PREP) were assessed and correlated. Patients were stratified for gender and disease severity as reflected by renal function. Results All Fabry patients (31 men, 45 women) had small fiber neuropathy. Men with Fabry disease showed impaired cold (p < 0.01) and warm perception (p < 0.05), while women did not differ from controls. Intraepidermal nerve fiber density (IENFD) was reduced at the lower leg (p < 0.001) and the back (p < 0.05) mainly of men with impaired renal function. When investigating A-delta fiber conduction with PREP, men but not women with Fabry disease had lower amplitudes upon stimulation at face (p < 0.01), hands (p < 0.05), and feet (p < 0.01) compared to controls. PREP amplitudes further decreased with advance in disease severity. PREP amplitudes and warm (p < 0.05) and cold detection thresholds (p < 0.01) at the feet correlated positively in male patients. Conclusion Small fiber conduction is impaired in men with Fabry disease and worsens with advanced disease severity. PREP are well-suited to measure A-delta fiber conduction.},
  language  = {en}
}
@article{ZhaoZhangBhuripanyoetal.2013,
  author    = {Zhao, Bo and Zhang, Keya and Bhuripanyo, Karan and Choi, Chan Hee J. and Villhauer, Eric B. and Li, Heng and Zheng, Ning and Kiyokawa, Hiroaki and Schindelin, Hermann and Yin, Jun},
  title     = {Profiling the Cross Reactivity of Ubiquitin with the Nedd8 Activating Enzyme by Phage Display},
  series = {PLoS ONE},
  volume    = {8},
  journal   = {PLoS ONE},
  number    = {e70312},
  issn      = {1932-6203},
  doi       = {10.1371/journal.pone.0070312},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-128479},
  year      = {2013},
  abstract  = {The C-terminal peptides of ubiquitin (UB) and UB-like proteins (UBLs) play a key role in their recognition by the specific activating enzymes (E1s) to launch their transfer through the respective enzymatic cascades thus modifying cellular proteins. UB and Nedd8, a UBL regulating the activity of cullin-RING UB ligases, only differ by one residue at their C-termini; yet each has its specific E1 for the activation reaction. It has been reported recently that UAE can cross react with Nedd8 to enable its passage through the UB transfer cascade for protein neddylation. To elucidate differences in UB recognition by UAE and NAE, we carried out phage selection of a UB library with randomized C-terminal sequences based on the catalytic formation of UB similar to NAE thioester conjugates. Our results confirmed the previous finding that residue 72 of UB plays a "gate-keeping" role in E1 selectivity. We also found that diverse sequences flanking residue 72 at the UB C-terminus can be accommodated by NAE for activation. Furthermore heptameric peptides derived from the C-terminal sequences of UB variants selected for NAE activation can function as mimics of Nedd8 to form thioester conjugates with NAE and the downstream E2 enzyme Ubc12 in the Nedd8 transfer cascade. Once the peptides are charged onto the cascade enzymes, the full-length Nedd8 protein is effectively blocked from passing through the cascade for the critical modification of cullin. We have thus identified a new class of inhibitors of protein neddylation based on the profiles of the UB C-terminal sequences recognized by NAE.},
  language  = {en}
}
@article{ZellerMuellerGutberletetal.2013,
  author    = {Zeller, Mario and M{\"u}ller, Alexander and Gutberlet, Marcel and Nichols, Thomas and Hahn, Dietbert and K{\"o}stler, Herbert and Bartsch, Andreas J.},
  title     = {Boosting BOLD fMRI by K-Space Density Weighted Echo Planar Imaging},
  series = {PLoS ONE},
  journal   = {PLoS ONE},
  doi       = {10.1371/journal.pone.0074501},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-97233},
  year      = {2013},
  abstract  = {Functional magnetic resonance imaging (fMRI) has become a powerful and influential method to non-invasively study neuronal brain activity. For this purpose, the blood oxygenation level-dependent (BOLD) effect is most widely used. T2* weighted echo planar imaging (EPI) is BOLD sensitive and the prevailing fMRI acquisition technique. Here, we present an alternative to its standard Cartesian recordings, i.e. k-space density weighted EPI, which is expected to increase the signal-to-noise ratio in fMRI data. Based on in vitro and in vivo pilot measurements, we show that fMRI by k-space density weighted EPI is feasible and that this new acquisition technique in fact boosted spatial and temporal SNR as well as the detection of local fMRI activations. Spatial resolution, spatial response function and echo time were identical for density weighted and conventional Cartesian EPI. The signal-to-noise ratio gain of density weighting can improve activation detection and has the potential to further increase the sensitivity of fMRI investigations.},
  language  = {en}
}
@phdthesis{Zeeb2013,
  author    = {Zeeb, Steffen},
  title     = {Chaos Synchronization in Time-Delayed Coupled Networks},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-78966},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2013},
  abstract  = {Die vorliegende Arbeit befasst sich mit der Untersuchung verschiedener Aspekte der Chaos Synchronisation von Netzwerken mit zeitverz{\"o}gerten Kopplungen. Ein Netzwerk aus identischen chaotischen Einheiten kann vollst{\"a}ndig und isochron synchronisieren, auch wenn der Signalaustausch einer starken Zeitverz{\"o}gerung unterliegt. Im ersten Teil der Arbeit werden Systeme mit mehreren Zeitverz{\"o}gerungen betrachtet. Dabei erstrecken sich die verschiedenen Zeitverz{\"o}gerungen jeweils {\"u}ber einen weiten Bereich an Gr{\"o}ßenordnungen. Es wird gezeigt, dass diese Zeitverz{\"o}gerungen im Lyapunov Spektrum des Systems auftreten; verschiedene Teile des Spektrums skalieren jeweils mit einer der Zeitverz{\"o}gerungen. Anhand des Skalierungsverhaltens des maximalen Lyapunov Exponenten k{\"o}nnen verschiedene Arten von Chaos definiert werden. Diese bestimmen die Synchronisationseigenschaften eines Netzwerkes und werden insbesondere wichtig bei hierarchischen Netzwerken, d.h. bei Netzwerken bestehend aus Unternetzwerken, bei welchen Signale innerhalb des Unternetzwerkes auf einer anderen Zeitskala ausgetauscht werden als zwischen verschiedenen Unternetzwerken. F{\"u}r ein solches System kann sowohl vollst{\"a}ndige als auch Unternetzwerksynchronisation auftreten. Skaliert der maximale Lyapunov Exponent mit der k{\"u}rzeren Zeitverz{\"o}gerung des Unternetzwerkes dann k{\"o}nnen nur die Elemente des Unternetzwerkes synchronisieren. Skaliert der maximale Lyapunov Exponent allerdings mit der l{\"a}ngeren Zeitverz{\"o}gerung kann das komplette Netzwerk vollst{\"a}ndig synchronisieren. Dies wird analytisch f{\"u}r die Bernoulli Abbildung und numerisch f{\"u}r die Zelt Abbildung gezeigt. Der zweite Teil befasst sich mit der Attraktordimension und ihrer {\"A}nderung am {\"U}bergang zur vollst{\"a}ndiger Chaos Synchronisation. Aus dem Lyapunov Spektrum des Systems wird die Kaplan-Yorke Dimension berechnet und es wird gezeigt, dass diese am Synchronisations{\"u}bergang aus physikalischen Gr{\"u}nden einen Sprung haben muss. Aus der Zeitreihe der Dynamik des Systems wird die Korrelationsdimension bestimmt und anschließend mit der Kaplan-Yorke Dimension verglichen. F{\"u}r Bernoulli Systeme finden wir in der Tat eine Diskontinuit{\"a}t in der Korrelationsdimension. Die St{\"a}rke des Sprungs der Kaplan-Yorke Dimension wird f{\"u}r ein Netzwerk aus Bernoulli Einheiten als Funktion der Netzwerkgr{\"o}ße berechnet. Desweiteren wird das Skalierungsverhalten der Kaplan-Yorke Dimension sowie der Kolmogoroventropie in Abh{\"a}ngigkeit der Systemgr{\"o}ße und der Zeitverz{\"o}gerung untersucht. Zu guter Letzt wird eine Verstimmung der Einheiten, d.h., ein "parameter mismatch", eingef{\"u}hrt und analysiert wie diese das Verhalten der Attraktordimension {\"a}ndert. Im dritten und letzten Teil wird die lineare Antwort eines synchronisierten chaotischen Systems auf eine kleine externe St{\"o}rung untersucht. Diese St{\"o}rung bewirkt eine Abweichung der Einheiten vom perfekt synchronisierten Zustand. Die Verteilung der Abst{\"a}nde zwischen zwei Einheiten dient als Maß f{\"u}r die lineare Antwort des Systems. Diese Verteilung sowie ihre Momente werden numerisch und f{\"u}r Spezialf{\"a}lle auch analytisch berechnet. Wir finden, dass im synchronisierten Zustand, in Abh{\"a}ngigkeit der Parameter des Systems, Verteilungen auftreten k{\"o}nnen die einem Potenzgesetz gehorchen und dessen Momente divergieren. Als weiteres Maß f{\"u}r die lineare Antwort wird die Bit Error Rate einer {\"u}bermittelten bin{\"a}ren Nachricht verwendet. The Bit Error Rate ist durch ein Integral {\"u}ber die Verteilung der Abst{\"a}nde gegeben. In dieser Arbeit wird sie vorwiegend numerisch untersucht und wir finden ein komplexes, nicht monotones Verhalten als Funktion der Kopplungsst{\"a}rke. F{\"u}r Spezialf{\"a}lle weist die Bit Error Rate eine "devil's staircase" auf, welche mit einer fraktalen Struktur in der Verteilung der Abst{\"a}nde verkn{\"u}pft ist. Die lineare Antwort des Systems auf eine harmonische St{\"o}rung wird ebenfalls untersucht. Es treten Resonanzen auf, welche in Abh{\"a}ngigkeit von der Zeitverz{\"o}gerung unterdr{\"u}ckt oder verst{\"a}rkt werden. Eine bi-direktional gekoppelte Kette aus drei Einheiten kann eine St{\"o}rung vollst{\"a}ndig heraus filtern, so dass die Bit Error Rate und auch das zweite Moment verschwinden.},
  subject      = {Chaostheorie},
  language  = {en}
}
@phdthesis{Zancolli2013,
  author    = {Zancolli, Giulia},
  title     = {Amphibian diversity along the slope of Mount Kilimanjaro: from species to genes},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-91792},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2013},
  abstract  = {1. Since the early nineteenth century describing (and understanding) patterns of distribution of biodiversity across the Earth has represented one of the most significant intellectual challenges to ecologists and biogeographers. Among the most striking patterns of species richness are: the latitudinal and elevational gradients, with peaks in number of species at low latitudes and somewhere at mid altitudes, although other patterns, e.g. declines with increasing elevation, are often observed. Even in highly diverse tropical regions, species richness is not evenly distributed but there are "hotspots" of biodiversity where an exceptional number of species, especially endemics, are concentrated. Unfortunately, such areas are also experiencing dramatic loss of habitat. Among vertebrate taxa, amphibians are facing the most alarming number of extinctions. Habitat destruction, pollution and emergence of infectious diseases such as chytridiomycosis, are causing worldwide population declines. Responses to these drivers can be multidirectional and subtle, i.e. they may not be captured at the species but at the genetic level. Moreover, present patterns of diversity can result from the influence of past geological, climatic and environmental changes. In this study, I used a multidisciplinary and multilevel approach to understand how and to which extent the landscape influences amphibian diversity. Mount Kilimanjaro is an exceptional tropical region where the landscape is rapidly evolving due to land use changes; additionally, there is a broad lack of knowledge of its amphibian fauna. During two rainy seasons in 2011, I recorded anurans from the foothills to 3500 m altitude; in addition, I focused on two river frog species and collected tissue samples for genetic analysis and swabs for detection of chytridiomycosis, the deadly disease caused by Batrachochytrium dendrobatidis (Bd). 2. I analyzed how species richness and composition change with increasing elevation and anthropogenic disturbance. In order to disentangle the observed patterns of species diversity and distribution, I incorporated inferences from historical biogeography and compared the assemblage of Mt. Kilimanjaro and Mt. Meru (both recent volcanoes) with those of the older Eastern Arc Mountains. Species richness decreased with elevation and locally increased in presence of water bodies, but I did not detect effects of either anthropogenic disturbance or vegetation structure on species richness and composition. Moreover, I found a surprisingly low number of forest species. Historical events seem to underlie the current pattern of species distribution; the young age of Mt. Kilimanjaro and the complex biogeographic processes which occurred in East Africa during the last 20 million years prevented montane forest frogs from colonizing the volcano. 3. I focused on the genetic level of biodiversity and investigated how the landscape, i.e. elevation, topographic relief and land cover, influence genetic variation, population structure and gene flow of two ecologically similar and closely related river frog species, namely Amietia angolensis and Amietia wittei. I detected greater genetic differentiation among populations in the highland species (A. wittei) and higher genetic variation in the lowland species (A. angolensis), although genetic diversity was not significantly correlated with elevation. Importantly, human settlements seemed to restrict gene flow in A. angolensis, whereas steep slopes were positively correlated with gene flow in A. wittei. This results show that even ecologically similar species can respond differently to landscape processes and that the spatial configuration of topographic features combined with species-specific biological attributes can affect dispersal and gene flow in disparate ways. 4. River frogs of the genus Amietia seem to be particularly susceptible to chytridiomycosis, showing the highest pathogen load in Kenya and other African countries. In the last study, I collected swab samples from larvae of A. angolensis and A. wittei for Bd detection. Both species resulted Bd-positive. The presence of Bd on Mt. Kilimanjaro has serious implication. For instance, Bd can be transported by footwear of hikers from contaminated water and soil. Tourists visiting Mt. Kilimanjaro may translocate Bd zoospores to other areas such as the nearby Eastern Arc Mts. where endemic and vulnerable species may still be na{\"i}ve to the fungus and thus suffer of population declines. 5. My study significantly contributed to the knowledge of the amphibian fauna of Mt. Kilimanjaro and of East Africa in general, and it represents a valuable tool for future conservation actions and measures. Finally, it highlights the importance of using a multidisciplinary (i.e. community ecology, historical biogeography, landscape genetics, disease ecology) and multilevel (i.e. community, species, population, gene) approach to disentangle patterns of biodiversity.},
  subject      = {Kilimandscharo},
  language  = {en}
}
@article{ZahnleiterUebeEkicietal.2013,
  author    = {Zahnleiter, Diana and Uebe, Steffen and Ekici, Arif B. and Hoyer, Juliane and Wiesener, Antje and Wieczorek, Dagmar and Kunstmann, Erdmute and Reis, Andr{\´e} and Doerr, Helmuth-Guenther and Rauch, Anita and Thiel, Christian T.},
  title     = {Rare Copy Number Variants Are a Common Cause of Short Stature},
  series = {PLoS Genetics},
  volume    = {9},
  journal   = {PLoS Genetics},
  number    = {3},
  issn      = {1553-7404},
  doi       = {10.1371/journal.pgen.1003365},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-127645},
  pages     = {e1003365},
  year      = {2013},
  abstract  = {Human growth has an estimated heritability of about 80\%-90\%. Nevertheless, the underlying cause of shortness of stature remains unknown in the majority of individuals. Genome-wide association studies (GWAS) showed that both common single nucleotide polymorphisms and copy number variants (CNVs) contribute to height variation under a polygenic model, although explaining only a small fraction of overall genetic variability in the general population. Under the hypothesis that severe forms of growth retardation might also be caused by major gene effects, we searched for rare CNVs in 200 families, 92 sporadic and 108 familial, with idiopathic short stature compared to 820 control individuals. Although similar in number, patients had overall significantly larger CNVs \((p-value <1 x 10^{-7})\). In a gene-based analysis of all non-polymorphic CNVs >50 kb for gene function, tissue expression, and murine knock-out phenotypes, we identified 10 duplications and 10 deletions ranging in size from 109 kb to 14 Mb, of which 7 were de novo (p < 0.03) and 13 inherited from the likewise affected parent but absent in controls. Patients with these likely disease causing 20 CNVs were smaller than the remaining group (p < 0.01). Eleven (55\%) of these CNVs either overlapped with known microaberration syndromes associated with short stature or contained GWAS loci for height. Haploinsufficiency (HI) score and further expression profiling suggested dosage sensitivity of major growth-related genes at these loci. Overall 10\% of patients carried a disease-causing CNV indicating that, like in neurodevelopmental disorders, rare CNVs are a frequent cause of severe growth retardation.},
  language  = {en}
}
@article{ZadehKhorasaniNolteMuelleretal.2013,
  author    = {Zadeh-Khorasani, Maryam and Nolte, Thomas and Mueller, Thomas D. and Pechlivanis, Markos and Rueff, Franziska and Wollenberg, Andreas and Fricker, Gert and Wolf, Eckhard and Siebeck, Matthias and Gropp, Roswitha},
  title     = {NOD-scid IL2R \(\gamma^{null}\) mice engrafted with human peripheral blood mononuclear cells as a model to test therapeutics targeting human signaling pathways},
  series = {Journal of Translational Medicine},
  volume    = {11},
  journal   = {Journal of Translational Medicine},
  number    = {4},
  issn      = {1479-5876},
  doi       = {10.1186/1479-5876-11-4},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-122960},
  year      = {2013},
  abstract  = {Background: Animal models of human inflammatory diseases have limited predictive quality for human clinical trials for various reasons including species specific activation mechanisms and the immunological background of the animals which markedly differs from the genetically heterogeneous and often aged patient population. Objective: Development of an animal model allowing for testing therapeutics targeting pathways involved in the development of Atopic Dermatitis (AD) with better translatability to the patient. Methods: NOD-scid IL2R \(\gamma^{null}\) mice engrafted with human peripheral blood mononuclear cells (hPBMC) derived from patients suffering from AD and healthy volunteers were treated with IL-4 and the antagonistic IL-4 variant R121/Y124D (Pitrakinra). Levels of human (h) IgE, amount of B-, T- and plasma-cells and ratio of CD4 : CD8 positive cells served as read out for induction and inhibition of cell proliferation and hIgE secretion. Results were compared to in vitro analysis. Results: hIgE secretion was induced by IL-4 and inhibited by the IL-4 antagonist Pitrakinra in vivo when formulated with methylcellulose. B-cells proliferated in response to IL-4 in vivo; the effect was abrogated by Pitrakinra. IL-4 shifted CD4 : CD8 ratios in vitro and in vivo when hPBMC derived from healthy volunteers were used. Pitrakinra reversed the effect. Human PBMC derived from patients with AD remained inert and engrafted mice reflected the individual responses observed in vitro. Conclusion: NOD-scid IL2R \(\gamma^{null}\) mice engrafted with human PBMC reflect the immunological history of the donors and provide a complementary tool to in vitro studies. Thus, studies in this model might provide data with better translatability from bench to bedside.},
  language  = {en}
}
@phdthesis{Ye2013,
  author    = {Ye, Yuxiang},
  title     = {Molecular and Cellular Magnetic Resonance Imaging of Myocardial Infarct Healing},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-72514},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2013},
  abstract  = {Myokardinfarkte (MI) sind eine der h{\"a}ufigsten Todesursachen weltweit. Eine rechtzeitige Wiederherstellung des koronaren Blutflusses im isch{\"a}mischen Myokard reduziert signifikant die Sterblichkeitsrate akuter Infarkte und vermindert das ventrikul{\"a}re Remodeling. {\"U}berlebende MI-Patienten entwickeln jedoch h{\"a}ufig eine Herzinsuffizienz, die mit einer reduzierten Lebensqualit{\"a}t, hohen Sterblichkeitsrate (10\% j{\"a}hrlich), sowie hohen Kosten f{\"u}r das Gesundheitssystem einhergeht. Die Entwicklung der Herzinsuffizienz nach einem MI ist auf den hohen Verlust kontraktiler Kardiomyozyten, w{\"a}hrend der Isch{\"a}mie-Reperfusion zur{\"u}ckzuf{\"u}hren. Anschließende komplexe strukturelle und funktionelle Ver{\"a}nderungen resultieren aus Modifikationen des infarzierten und nicht infarzierten Myokards auf molekularer und zellul{\"a}rer Ebene. Die verbesserte {\"U}berlebensrate von Patienten mit akutem MI und das Fehlen effizienter Therapien, die die Entwicklung und das Fortschreiten des ventrikul{\"a}ren Remodelings verhindern, f{\"u}hren zu einer hohen Pr{\"a}valenz der Herzinsuffizienz. Die kardiale Magnetresonanztomographie (MRT) ist eine wichtige Methode zur Diagnose und Beurteilung des Myokardinfarktes. Mit dem technologischen Fortschritt wurden die Grenzen der MRT erweitert, so dass es heute m{\"o}glich ist, auch molekulare und zellul{\"a}re Ereignisse in vivo und nicht-invasiv zu untersuchen. In Kombination mit kardialer Morphologie und Funktion k{\"o}nnte die Visualisierung essentieller molekularer und zellul{\"a}rer Marker in vivo weitreichende Einblicke in den Heilungsprozess infarzierter Herzen liefern, was zu neuen Erkenntnissen f{\"u}r ein besseres Verst{\"a}ndnis und bessere Therapien des akuten MI f{\"u}hren k{\"o}nnte. In dieser Arbeit wurden Methoden f{\"u}r die molekulare und zellul{\"a}re kardiale MRT-Bildgebung der Inflammation und des Kalziumstroms im Heilungsprozess des akuten Myokardinfarktes in vivo in einem Rattenmodel mit klinischer Relevanz etabliert.},
  subject      = {Kernspintomografie},
  language  = {en}
}
@article{YanHongChenetal.2013,
  author    = {Yan, Yan and Hong, Ni and Chen, Tiansheng and Li, Mingyou and Wang, Tiansu and Guan, Guijun and Qiao, Yongkang and Chen, Songlin and Schartl, Manfred and Li, Chang-Ming and Hong, Yunhan},
  title     = {p53 Gene Targeting by Homologous Recombination in Fish ES Cells},
  series = {PLoS One},
  volume    = {8},
  journal   = {PLoS One},
  number    = {3},
  doi       = {10.1371/journal.pone.0059400},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-133416},
  pages     = {e59400},
  year      = {2013},
  abstract  = {Background: Gene targeting (GT) provides a powerful tool for the generation of precise genetic alterations in embryonic stem (ES) cells to elucidate gene function and create animal models for human diseases. This technology has, however, been limited to mouse and rat. We have previously established ES cell lines and procedures for gene transfer and selection for homologous recombination (HR) events in the fish medaka (Oryzias latipes). Methodology and Principal Findings: Here we report HR-mediated GT in this organism. We designed a GT vector to disrupt the tumor suppressor gene p53 (also known as tp53). We show that all the three medaka ES cell lines, MES1 similar to MES3, are highly proficient for HR, as they produced detectable HR without drug selection. Furthermore, the positive-negative selection (PNS) procedure enhanced HR by similar to 12 folds. Out of 39 PNS-resistant colonies analyzed, 19 (48.7\%) were positive for GT by PCR genotyping. When 11 of the PCR-positive colonies were further analyzed, 6 (54.5\%) were found to be bona fide homologous recombinants by Southern blot analysis, sequencing and fluorescent in situ hybridization. This produces a high efficiency of up to 26.6\% for p53 GT under PNS conditions. We show that p53 disruption and long-term propagation under drug selection conditions do not compromise the pluripotency, as p53-targeted ES cells retained stable growth, undifferentiated phenotype, pluripotency gene expression profile and differentiation potential in vitro and in vivo. Conclusions: Our results demonstrate that medaka ES cells are proficient for HR-mediated GT, offering a first model organism of lower vertebrates towards the development of full ES cell-based GT technology.},
  language  = {en}
}
@phdthesis{Wu2013,
  author    = {Wu, Lingdan},
  title     = {Emotion Regulation in Addicted Smokers},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-85471},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2013},
  abstract  = {Background: Nicotine addiction is the most prevalent type of drug addiction that has been described as a cycle of spiraling dysregulation of the brain reward systems. Imaging studies have shown that nicotine addiction is associated with abnormal function in prefrontal brain regions that are important for cognitive emotion regulation. It was assumed that addicts may perform less well than healthy nonsmokers in cognitive emotion regulation tasks. The primary aims of this thesis were to investigate emotional responses to natural rewards among smokers and nonsmokers and to determine whether smokers differ from nonsmokers in cognitive regulation of positive and negative emotions. To address these aims, two forms of appraisal paradigms (i.e., appraisal frame and reappraisal) were applied to compare changes in emotional responses of smokers with that of nonsmokers as a function of appraisal strategies. Experiment 1: The aim of the first experiment was to evaluate whether and how appraisal frames preceding positive and negative picture stimuli affect emotional experience and facial expression of individuals. Twenty participants were exposed to 125 pairs of auditory appraisal frames (either neutral or emotional) followed by picture stimuli reflecting five conditions: unpleasant-negative, unpleasant-neutral, pleasant-positive, pleasant-neutral and neutral-neutral. Ratings of valence and arousal as well as facial EMG activity over the corrugator supercilii and the zygomaticus major were measured simultaneously. The results indicated that appraisal frames could alter both subjective emotional experience and facial expressions, irrespective of the valence of the pictorial stimuli. These results suggest and support that appraisal frame is an efficient paradigm in regulation of multi-level emotional responses. 8 Experiment 2: The second experiment applied the appraisal frame paradigm to investigate how smokers differ from nonsmokers on cognitive emotion regulation. Sixty participants (22 nonsmokers, 19 nondeprived smokers and 19 12-h deprived smokers) completed emotion regulation tasks as described in Experiment 1 while emotional responses were concurrently recorded as reflected by self-ratings and psychophysiological measures (i.e., facial EMG and EEG). The results indicated that there was no group difference on emotional responses to natural rewards. Moreover, nondeprived smokers and deprived smokers performed as well as nonsmokers on the emotion regulation task. The lack of group differences in multiple emotional responses (i.e., self-reports, facial EMG activity and brain EEG activity) suggests that nicotine addicts have no deficit in cognitive emotion regulation of natural rewards via appraisal frames. Experiment 3: The third experiment aimed to further evaluate smokers' emotion regulation ability by comparing performances of smokers and nonsmokers in a more challenging cognitive task (i.e., reappraisal task). Sixty-five participants (23 nonsmokers, 22 nondeprived smokers and 20 12-h deprived smokers) were instructed to regulate emotions by imagining that the depicted negative or positive scenario would become less negative or less positive over time, respectively. The results showed that nondeprived smokers and deprived smokers responded similarly to emotional pictures and performed as well as nonsmokers in down-regulating positive and negative emotions via the reappraisal strategy. These results indicated that nicotine addicts do not have deficit in emotion regulation using cognitive appraisal strategies. In sum, the three studies consistently revealed that addicted smokers were capable to regulate emotions via appraisal strategies. This thesis establishes the groundwork for therapeutic use of appraisal instructions to cope with potential self-regulation failures in nicotine addicts.},
  subject      = {Gef{\"u}hl},
  language  = {en}
}