@article{SchuetzeRoehringVorlovaetal.2015,
  author    = {Sch{\"u}tze, Friedrich and R{\"o}hring, Florian and Vorlov{\´a}, Sandra and G{\"a}tzner, Sabine and Kuhn, Anja and Erg{\"u}n, S{\"u}leyman and Henke, Erik},
  title     = {Inhibition of lysyl oxidases improves drug diffusion and increases efficacy of cytotoxic treatment in 3D tumor models},
  series = {Scientific Reports},
  volume    = {5},
  journal   = {Scientific Reports},
  number    = {17576},
  doi       = {10.1038/srep17576},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-145109},
  year      = {2015},
  abstract  = {Tumors are characterized by a rigid, highly cross-linked extracellular matrix (ECM), which impedes homogeneous drug distribution and potentially protects malignant cells from exposure to therapeutics. Lysyl oxidases are major contributors to tissue stiffness and the elevated expression of these enzymes observed in most cancers might influence drug distribution and efficacy. We examined the effect of lysyl oxidases on drug distribution and efficacy in 3D in vitro assay systems. In our experiments elevated lysyl oxidase activity was responsible for reduced drug diffusion under hypoxic conditions and consequently impaired cytotoxicity of various chemotherapeutics. This effect was only observed in 3D settings but not in 2D-cell culture, confirming that lysyl oxidases affect drug efficacy by modification of the ECM and do not confer a direct desensitizing effect. Both drug diffusion and efficacy were strongly enhanced by inhibition of lysyl oxidases. The results from the in vitro experiments correlated with tumor drug distribution in vivo, and predicted response to therapeutics in murine tumor models. Our results demonstrate that lysyl oxidase activity modulates the physical barrier function of ECM for small molecule drugs influencing their therapeutic efficacy. Targeting this process has the potential to significantly enhance therapeutic efficacy in the treatment of malignant diseases.},
  language  = {en}
}
@phdthesis{Rehman2018,
  author    = {Rehman, Saba},
  title     = {Identification of accessible and closed substrate binding sites in the outward open cleft of rat Organic Cation Transporter 1 (rOCT1)},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-169992},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2018},
  abstract  = {The present study was conducted on the rOCT1, a member of SLC22 family. Structurally, it consists of 12 membrane spanning α-helices with both N- and C-termini intracellular. Studies done so far, through tracer uptake and inhibition, reconstitution of rOCT1 in nanodiscs and proteoliposomes and voltage-clamp fluorometry, have identified the main amino acids in the cleft of rOCT1 that interact in a critical manner with the substrates/inhibitors either directly or indirectly. Homology modeling studies have also supported these observations. In the present study we aimed at measuring the binding of substrates MPP+ and TEA+ to rOCT1 at 0oC in order to establish the amino acids in the cleft region that interact with the substrate when the transporter is frozen in the outward-open conformation. Previously identified crucial amino acids (Asp475, Phe160, Leu447, Arg440, Trp218 and Tyr222) were selected for the study. rOCT1 wild-type and its mutants were stably expressed in HEK293 cells and these cells were used for the binding measurements with the radioactive substrate (MPP+ or TEA+) at 0°C in Mg-Ca-PBS buffer as described in "Materials and Methods" section in detail. rOCT1 wild-type revealed for MPP+-binding a KD which was not significantly different from the corresponding Km value. Also, after addition of 10 nM non-radioactive MPP+, an initial increase of about 20\% in bound MPP+ was observed. The results indicate that the Km for transport is dependent on the binding of MPP+ to the outward-open conformation and hints at the possibility of allosteric interaction between the binding sites. Mutations at position Trp218, Phe160 and Asp475 resulted in a change in the KD value. Trp218 mutations also showed an allosteric increase similar to the rOCT1 wild-type. This study suggests that these amino acids are located at a critical position in the outward-open conformation for MPP+ transport. TEA+-binding could not be observed in rOCT1 wild-type, indicating that the binding site is perhaps inaccessible for TEA+ in frozen outward-open state. The mutants D475E, F160A, L447F, R440K and Y222F showed a very low affinity binding with a very high KD value as compared to the corresponding Km values indicating that the transporter might have different affinities for extra-cellular binding alone and for the complete transport process especially if temperature is the limiting factor. Substrate inhibition studies done using both MPP+ and TEA+ have confirmed the existence of overlapping binding sites for these two ligands. This study has confirmed the direct interaction of Trp218, Phe160, Asp475 with MPP+ and Phe160, Asp475, Leu447, Arg440 and Tyr222 with TEA+ in the outward-open conformation.},
  subject      = {Kation},
  language  = {en}
}
@article{WernerWakabayashiBaueretal.2018,
  author    = {Werner, Rudolf and Wakabayashi, Hiroshi and Bauer, Jochen and Sch{\"u}tz, Claudia and Zechmeister, Christina and Hayakawa, Nobuyuki and Javadi, Mehrbod S. and Lapa, Constantin and Jahns, Roland and Erg{\"u}n, S{\"u}leyman and Jahns, Valerie and Higuchi, Takahiro},
  title     = {Longitudinal \(^{18}\)F-FDG PET imaging in a Rat Model of Autoimmune Myocarditis},
  series = {European Heart Journal Cardiovascular Imaging},
  journal   = {European Heart Journal Cardiovascular Imaging},
  issn      = {2047-2404},
  doi       = {10.1093/ehjci/jey119},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-165601},
  pages     = {1-8},
  year      = {2018},
  abstract  = {Aims: Although mortality rate is very high, diagnosis of acute myocarditis remains challenging with conventional tests. We aimed to elucidate the potential role of longitudinal 2-Deoxy-2-\(^{18}\)F-fluoro-D-glucose (\(^{18}\)F-FDG) positron emission tomography (PET) inflammation monitoring in a rat model of experimental autoimmune myocarditis. Methods and results: Autoimmune myocarditis was induced in Lewis rats by immunizing with porcine cardiac myosin emulsified in complete Freund's adjuvant. Time course of disease was assessed by longitudinal \(^{18}\)F-FDG PET imaging. A correlative analysis between in- and ex vivo \(^{18}\)F-FDG signalling and macrophage infiltration using CD68 staining was conducted. Finally, immunohistochemistry analysis of the cell-adhesion markers CD34 and CD44 was performed at different disease stages determined by longitudinal \(^{18}\)F-FDG PET imaging. After immunization, myocarditis rats revealed a temporal increase in 18F-FDG uptake (peaked at week 3), which was followed by a rapid decline thereafter. Localization of CD68 positive cells was well correlated with in vivo \(^{18}\)F-FDG PET signalling (R\(^2\) = 0.92) as well as with ex vivo 18F-FDG autoradiography (R\(^2\) = 0.9, P < 0.001, respectively). CD44 positivity was primarily observed at tissue samples obtained at acute phase (i.e. at peak 18F-FDG uptake), while CD34-positive staining areas were predominantly identified in samples harvested at both sub-acute and chronic phases (i.e. at \(^{18}\)F-FDG decrease). Conclusion: \(^{18}\)F-FDG PET imaging can provide non-invasive serial monitoring of cardiac inflammation in a rat model of acute myocarditis.},
  subject      = {Myokarditis},
  language  = {en}
}
@unpublished{NoseWernerUedaetal.2018,
  author    = {Nose, Naoko and Werner, Rudolf A. and Ueda, Yuichiro and G{\"u}nther, Katharina and Lapa, Constantin and Javadi, Mehrbod S. and Fukushima, Kazuhito and Edenhofer, Frank and Higuchi, Takahiro},
  title     = {Metabolic substrate shift in human induced pluripotent stem cells during cardiac differentiation: Functional assessment using in vitro radionuclide uptake assay},
  series = {International Journal of Cardiology},
  journal   = {International Journal of Cardiology},
  issn      = {0167-5273},
  doi       = {10.1016/j.ijcard.2018.06.089},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-163320},
  year      = {2018},
  abstract  = {Background: Recent developments in cellular reprogramming technology enable the production of virtually unlimited numbers of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM). Although hiPSC-CM share various characteristic hallmarks with endogenous cardiomyocytes, it remains a question as to what extent metabolic characteristics are equivalent to mature mammalian cardiomyocytes. Here we set out to functionally characterize the metabolic status of hiPSC-CM in vitro by employing a radionuclide tracer uptake assay. Material and Methods: Cardiac differentiation of hiPSC was induced using a combination of well-orchestrated extrinsic stimuli such as WNT activation (by CHIR99021) and BMP signalling followed by WNT inhibition and lactate based cardiomyocyte enrichment. For characterization of metabolic substrates, dual tracer uptake studies were performed with \(^{18}\)F-2-fluoro-2-deoxy-D-glucose (\(^{18}\)F-FDG) and \(^{125}\)I-β-methyl-iodophenyl-pentadecanoic acid (\(^{125}\)I-BMIPP) as transport markers of glucose and fatty acids, respectively. Results: After cardiac differentiation of hiPSC, in vitro tracer uptake assays confirmed metabolic substrate shift from glucose to fatty acids that was comparable to those observed in native isolated human cardiomyocytes. Immunostaining further confirmed expression of fatty acid transport and binding proteins on hiPSC-CM. Conclusions: During in vitro cardiac maturation, we observed a metabolic shift to fatty acids, which are known as a main energy source of mammalian hearts, suggesting hi-PSC-CM as a potential functional phenotype to investigate alteration of cardiac metabolism in cardiac diseases. Results also highlight the use of available clinical nuclear medicine tracers as functional assays in stem cell research for improved generation of autologous differentiated cells for numerous biomedical applications.},
  subject      = {Stammzelle},
  language  = {en}
}
@article{SagivMichaeliAssietal.2015,
  author    = {Sagiv, Jitka Y. and Michaeli, Janna and Assi, Simaan and Mishalian, Inbal and Kisos, Hen and Levy, Liran and Damti, Pazzit and Lumbroso, Delphine and Polyansky, Lola and Sionov, Ronit V. and Ariel, Amiram and Hovav, Avi-Hai and Henke, Erik and Fridlender, Zvi G. and Granot, Zvi},
  title     = {Phenotypic diversity and plasticity in circulating neutrophil subpopulations in cancer},
  series = {Cell Reports},
  volume    = {10},
  journal   = {Cell Reports},
  number    = {4},
  doi       = {10.1016/j.celrep.2014.12.039},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-144102},
  pages     = {562-573},
  year      = {2015},
  abstract  = {Controversy surrounds neutrophil function in cancer because neutrophils were shown to provide both pro-and antitumor functions. We identified a heterogeneous subset of low-density neutrophils (LDNs) that appear transiently in self-resolving inflammation but accumulate continuously with cancer progression. LDNs display impaired neutrophil function and immunosuppressive properties, characteristics that are in stark contrast to those of mature, high-density neutrophils (HDNs). LDNs consist of both immature myeloid-derived suppressor cells (MDSCs) and mature cells that are derived from HDNs in a TGF-beta-dependent mechanism. Our findings identify three distinct populations of circulating neutrophils and challenge the concept that mature neutrophils have limited plasticity. Furthermore, our findings provide a mechanistic explanation to mitigate the controversy surrounding neutrophil function in cancer.},
  language  = {en}
}
@phdthesis{Guenther2018,
  author    = {G{\"u}nther, Katharina},
  title     = {Generation of early human neuroepithelial progenitors from primary cells for biomedical applications},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-150348},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2018},
  abstract  = {Patient-specific induced pluripotent stem cells (iPSCs) emerged as a promising cell source for disease modeling and drug screening as well as a virtually unlimited source for restorative therapy. The thesis deals with three major topics to help realizing biomedical applications with neural stem cells. To enable the generation of transgene-free iPSCs, alternatives to retroviral reprogramming were developed. Hence, the adaptation and evaluation of reprogramming using excisable lentiviral constructs, Sendai virus (SeV) and synthetic mRNA-based methods was assessed in the first part of this thesis. hiPSCs exhibit the pluripotency markers OCT4, SSEA-4, TRA1-60 which were confirmed by immunofluorescence and flow cytometry. Besides, the potential to differentiate in cell types of all three germ layers was detected, confirming pluripotent identity of proliferating colonies resulting from various reprogramming strategies. However, major differences such as high efficiency with SeV in contrast to a relatively low efficiency with mRNA in regard to passage number and the phenotype of starting fibroblasts were observed. Furthermore, a prolonged clone- and passage-dependent residual presence of viral RNA genes was identified in SeV-iPSCs for up to 23 passages using RT-PCR underlining the importance of careful monitoring of clone selection. In contrast, viral-free reprogramming by synthetic mRNA represents a fully non-integrative approach but requires further refinement to be efficiently applicable to all fibroblasts. The second part of this thesis deals with the establishment of a rapid monolayer approach to differentiate neural progenitor cells from iPSCs. To achieve this, a two-step protocol was developed allowing first the formation of a stable, primitive NPC line within 7 days which was expanded for 2-3 passages. In a second step, a subsequent adaptation to conditions yielding neural rosette-like NPCs followed. Both neural lines were demonstrated to be expandable, cryopreservable and negative for the pluripotency marker OCT4. Furthermore, a neural precursor identity including SOX1, SOX2, PAX6, Nestin was confirmed by immunofluorescence and quantitative RT-PCR. Moreover, the differentiation resulted in TUJ1-positive neurons and GFAP-positive astrocytes. Nonetheless, the outcome of glial differentiation from primitive NSCs remained low, whereas FGF/EGF-NPCs were efficiently differentiated into GFAP-positive astrocytes which were implicated in a cellular model of the blood brain barrier. The third and major objective of this study was to generate human early neural progenitor cells from fetal brain tissue with a wide neural differentiation capacity. Therefore, a defined medium composition including small molecules and growth factors capable of modulation of crucial signaling pathways orchestrating early human development such as SHH and FGF was assessed. Indeed, specific culture conditions containing TGFβ inhibitor SB431542, SHH agonist Purmorphamine, GSK3β inhibitor CHIR99021 and basic FGF, but no EGF enabled robust formation of early neuroepithelial progenitor (eNEP) colonies displaying a homogeneous morphology and a high proliferation rate. Moreover, primary eNEPs exhibit a relatively high clonogenicity of more than 23 \% and can be monoclonally expanded for more than 45 passages carrying a normal karyotype. Characterization by immunofluorescence, flow cytometry and quantitative RT-PCR revealed a distinct NPC profile including SOX1, PAX6, Nestin and SOX2 and Prominin. Furthermore, primary eNEPs show NOTCH and HES5 activation in combination with non-polarized morphology, indicative of an early neuroepithelial identity. Microarray analysis unraveled SOX11, BRN2 and other HES-genes as characteristic upregulated genes. Interestingly, eNEPs were detected to display ventral midbrain/hindbrain regional identity. The validation of yielded cell types upon differentiation indicates a strong neurogenic potential with more than 90 \% of TUJ1-positive neurons. Moreover, astrocytes marked by GFAP and putative myelin structures indicating oligodendrocytes were identified. Electrophysiological recordings revealed functionally active neurons and immunofluorescence indicate GABAergic, glutamatergic, dopaminergic and serotonergic subtypes. Additionally, putative physiological synapse formation was observed by the presence of Synapsin and PSD-95 as well as by ultrastructural examination. Notably, rare neurons stained positive for the peripheral neuronal marker Peripherin suggesting the potential of eNEPS to give rise to cells of neural tube and neural crest origin. By the application of specific differentiation protocols an increase of TH-positive neurons or neural crest-derivatives such as putative A- and C-sensory neurons and mesenchymal cells was identified. Taken together, primary eNEPs might help to elucidate mechanisms of early human neurodevelopment and will serve as a novel source for cell replacement and further biomedical applications.},
  subject      = {progenitors},
  language  = {en}
}
@article{SchuetzJurastowBaderetal.2015,
  author    = {Sch{\"u}tz, Burkhard and Jurastow, Innokentij and Bader, Sandra and Ringer, Cornelia and Engelhardt, Jakob von and Chubanov, Vladimir and Gudermann, Thomas and Diener, Martin and Kummer, Wolfgang and Krasteva-Christ, Gabriela and Weihe, Eberhard},
  title     = {Chemical coding and chemosensory properties of cholinergic brush cells in the mouse gastrointestinal and biliary tract},
  series = {Frontiers in Physiology},
  volume    = {6},
  journal   = {Frontiers in Physiology},
  number    = {87},
  doi       = {10.3389/fphys.2015.00087},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-143550},
  year      = {2015},
  abstract  = {The mouse gastro-intestinal and biliary tract mucosal epithelia harbor choline acetyltransferase (ChAT)-positive brush cells with taste cell-like traits. With the aid of two transgenic mouse lines that express green fluorescent protein (EGFP) under the control of the ChAT promoter (EGFP\(^{ChAT}\)) and by using in situ hybridization and immunohistochemistry we found that EGFP\(^{ChAT}\) cells were clustered in the epithelium lining the gastric groove. EGFP\(^{ChAT}\) cells were numerous in the gall bladder and bile duct, and found scattered as solitary cells along the small and large intestine. While all EGFP\(^{ChAT}\) cells were also ChAT-positive, expression of the high-affinity choline transporter (ChT1) was never detected. Except for the proximal colon, EGFP\(^{ChAT}\) cells also lacked detectable expression of the vesicular acetylcholine transporter (VAChT). EGFP\(^{ChAT}\) cells were found to be separate from enteroendocrine cells, however they were all immunoreactive for cytokeratin 18 (CK18), transient receptor potential melastatin-like subtype 5 channel (TRPM5), and for cyclooxygenases 1 (COX1) and 2 (COX2). The ex vivo stimulation of colonic EGFP\(^{ChAT}\) cells with the bitter substance denatonium resulted in a strong increase in intracellular calcium, while in other epithelial cells such an increase was significantly weaker and also timely delayed. Subsequent stimulation with cycloheximide was ineffective in both cell populations. Given their chemical coding and chemosensory properties, EGFP\(^{ChAT}\) brush cells thus may have integrative functions and participate in induction of protective reflexes and inflammatory events by utilizing ACh and prostaglandins for paracrine signaling.},
  language  = {en}
}
@inproceedings{WernerWakabayashiJahnsetal.2017,
  author    = {Werner, Rudolf and Wakabayashi, Hiroshi and Jahns, Roland and Erg{\"u}n, S{\"u}leyman and Jahns, Valerie and Higuchi, Takahiro},
  title     = {PET-Guided Histological Characterization of Myocardial Infiltrating Cells in a Rat Model of Myocarditis},
  series = {European Heart Journal - Cardiovascular Imaging},
  volume    = {18},
  booktitle = {European Heart Journal - Cardiovascular Imaging},
  number    = {Supplement},
  publisher = {Oxford University Press},
  issn      = {2047-2404},
  doi       = {10.1093/ehjci/jex071},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-161127},
  pages     = {i1-i3},
  year      = {2017},
  abstract  = {No abstract available.},
  subject      = {Myokarditis},
  language  = {en}
}
@article{DrenckhahnDrenckhahn2018,
  author    = {Drenckhahn, Detlev and Drenckhahn, Helga},
  title     = {Trifolium micranthum Viv. an Nordseedeichen von Schleswig-Holstein - Charakterisierung der Pflanzen und ihrer Habitate, Status in Deutschland und Nachbargebieten},
  series = {Forum Geobotanicum},
  volume    = {8},
  journal   = {Forum Geobotanicum},
  issn      = {1867-9315},
  doi       = {10.3264/FG.2018.0308},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-159163},
  pages     = {1-13},
  year      = {2018},
  abstract  = {In der vorliegenden Arbeit wird ein neues Teilareal von T. micranthum mit zahlreichen Vorkommen an den Nordseedeichen von Schleswig-Holstein zwischen der Elbe{\"a}stuar und der Insel Nordstrand mit Schwerpunkt auf der Halbinsel Eiderstedt mitgeteilt, das geographisch zwischen dem Vorkommen in den Niederlanden und dem Ostsee-Areal in D{\"a}nemark vermittelt. Es handelt sich um die einzigen weitgehend naturnahen Wuchsorte der Art in Deutschland. Die anderen beiden aktuellen deutschen Vorkommen befinden sich auf Friedh{\"o}fen in Nordrhein-Westfalen. T. micranthum w{\"a}chst bevorzugt an den steilen und artenreicheren Innenb{\"o}schungen der Seedeiche, deren Vegetation durch intensive Schafbeweidung und Trittspuren kurz und l{\"u}ckig gehalten wird. Die Beweidung bewirkt eine signifikante Gr{\"o}ßenreduktion (Miniaturisierung) verschiedener Pflanzenteile. Widerspr{\"u}chliche Angaben zu bestimmungskritischen Merkmalen werden durch morphometrische Untersuchungen {\"u}berpr{\"u}ft. Unter anderem betr{\"a}gt die L{\"a}nge der Bl{\"u}tenstiele 0,6-1,1 mm (im Mittel 0,8 mm) und die Bl{\"u}ten mit Kelch sind deutlich unter 3 mm lang (im Mittel 2,4 mm). Die Zahl der Bl{\"u}ten der Infloreszenz betr{\"a}gt (1)2-6(8). Eine graphische Darstellung soll bei Artbestimmung und Auffinden neuer Wuchsorte behilflich sein.},
  subject      = {Klee},
  language  = {de}
}
@article{BailNotzRovitusoetal.2017,
  author    = {Bail, Kathrin and Notz, Quirin and Rovituso, Damiano M. and Schampel, Andrea and Wunsch, Marie and Koeniger, Tobias and Schropp, Verena and Bharti, Richa and Scholz, Claus-Juergen and Foerstner, Konrad U. and Kleinschnitz, Christoph and Kuerten, Stefanie},
  title     = {Differential effects of FTY720 on the B cell compartment in a mouse model of multiple sclerosis.},
  series = {Journal of Neuroinflammation},
  volume    = {14},
  journal   = {Journal of Neuroinflammation},
  number    = {148},
  doi       = {10.1186/s12974-017-0924-4},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-157869},
  year      = {2017},
  abstract  = {Background: MP4-induced experimental autoimmune encephalomyelitis (EAE) is a mouse model of multiple sclerosis (MS), which enables targeted research on B cells, currently much discussed protagonists in MS pathogenesis. Here, we used this model to study the impact of the S1P1 receptor modulator FTY720 (fingolimod) on the autoreactive B cell and antibody response both in the periphery and the central nervous system (CNS). Methods: MP4-immunized mice were treated orally with FTY720 for 30 days at the peak of disease or 50 days after EAE onset. The subsequent disease course was monitored and the MP4-specific B cell/antibody response was measured by ELISPOT and ELISA. RNA sequencing was performed to determine any effects on B cell-relevant gene expression. S1P\(_{1}\) receptor expression by peripheral T and B cells, B cell subset distribution in the spleen and B cell infiltration into the CNS were studied by flow cytometry. The formation of B cell aggregates and of tertiary lymphoid organs (TLOs) was evaluated by histology and immunohistochemistry. Potential direct effects of FTY720 on B cell aggregation were studied in vitro. Results: FTY720 significantly attenuated clinical EAE when treatment was initiated at the peak of EAE. While there was a significant reduction in the number of T cells in the blood after FTY720 treatment, B cells were only slightly diminished. Yet, there was evidence for the modulation of B cell receptor-mediated signaling upon FTY720 treatment. In addition, we detected a significant increase in the percentage of B220\(^{+}\) B cells in the spleen both in acute and chronic EAE. Whereas acute treatment completely abrogated B cell aggregate formation in the CNS, the numbers of infiltrating B cells and plasma cells were comparable between vehicle- and FTY720-treated mice. In addition, there was no effect on already developed aggregates in chronic EAE. In vitro B cell aggregation assays suggested the absence of a direct effect of FTY720 on B cell aggregation. However, FTY720 impacted the evolution of B cell aggregates into TLOs. Conclusions: The data suggest differential effects of FTY720 on the B cell compartment in MP4-induced EAE.},
  language  = {en}
}
@misc{DrenckhahnBaumgartnerZonneveld2017,
  author    = {Drenckhahn, Detlev and Baumgartner, Werner and Zonneveld, Ben},
  title     = {Forum Geobotanicum Vol. 7 (2016/2017)},
  volume    = {7(2016/2017)},
  editor    = {Meierott, Lenz and Drenckhahn, Detlev and Dunkel, Franz G. and Ewald, J{\"o}rg and Schuhwerk, Franz},
  issn      = {1867-9315},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-157381},
  year      = {2017},
  abstract  = {Forum Geobotanicum is an electronic journal devoted to disseminate information concerning geographical distribution, ecology, morphology, taxonomy and conservation of vascular plants in the European Union with a main focus on middle Europe. It covers from molecular biology to environmental aspects. The focus is to publish original papers, reviews and announcements for the educated generalist as well as the specialist in this broad field. Forum Geobotanicum does not aim to supplant existing paper journals, but will be much more flexible in format, publication time and world-wide distribution than paper journals. Many important studies are being currently published in local journals and booklets and some of them are published privately. Hence, these studies will become aware to only a limited readership. Forum Geobotanicum will encourage authors of such papers to submit them as special issues of the journal. Moreover, the journal is planning to build up an E-mail-address section to support communication between geobotanists in Europe. The editors are optimistic that this electronic journal will develop to a widely used communication forum that will help to stimulate activities in the entire field of geobotany in middle Europe. To overcome problems of long term archivation and effective taxonomic publication of articles published electronically in Forum Geobotanicum, print versions of each volume of the journal and appropriate digital storage devices will be delivered freely to selected university libraries and state libraries in middle Europe.},
  language  = {mul}
}
@article{DrenckhahnZonneveld2017,
  author    = {Drenckhahn, Detlev and Zonneveld, Ben},
  title     = {Rubus viridilucidus Drenckhahn, eine neue Brombeerart aus der Sektion Corylifolii, Serie Subcanescentes},
  series = {Forum Geobotanicum},
  volume    = {7},
  journal   = {Forum Geobotanicum},
  issn      = {1867-9315},
  doi       = {10.3264/FG.2017.1221},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-156257},
  pages     = {34-42},
  year      = {2017},
  abstract  = {Rubus viridilucidus Drenckhahn ist eine tetraploide Brombeerart (2n=28) aus der Sektion Corylifolii, Serie Subcanescentes mit einem Genomgewicht (2C-Wert) von 1,49 pg, das dem Genomgewicht verwandter Sippen der Serie Subcanescentes wie R. scabrosus, R. fasciculatiformis und R. fasciculatus (1,52-1,54 pg) aus Unterfranken entspricht. Charakteristische Merkmale sind 3-4(5)-z{\"a}hlige Bl{\"a}tter mit herab gekr{\"u}mmten rundlichen bis breit obovaten Endbl{\"a}ttchen und breitovalen Seitenbl{\"a}ttchen, die eine v{\"o}llig unbehaarte, lichtgr{\"u}ne, mattgl{\"a}nzende Blattoberfl{\"a}che besitzen mit kontrastierender hell gr{\"u}nlich-grauer, samtig behaarter Blattunterseite. Die {\"u}berwiegend rundlichen bis stumpf kantigen, lichtgr{\"u}nen bis r{\"o}tlich {\"u}berlaufenen Sch{\"o}sslinge sind unbehaart und sp{\"a}rlich mit kurzen (<4mm) nadelf{\"o}rmigen Stacheln und wenigen Stieldr{\"u}sen besetzt. R. viridilucidus entwickelt zus{\"a}tzlich zu den Bl{\"u}tenzweigen der zweij{\"a}hrigen Sch{\"o}sslinge (Ausbreitungssch{\"o}sslinge) einen besonderen bl{\"u}henden 0,8 bis 1,6 m langen Sch{\"o}sslingstyp aus, den Rispensch{\"o}ssling, der direkt aus dem Wurzelstock entspringt und terminal in eine Bl{\"u}tenrispe ausl{\"a}uft. Bei R. viridilucidus sind zwei verschiedene Typen von Rispensch{\"o}sslingen ausgebildet. Die Sippe w{\"a}chst bevorzugt auf gest{\"o}rten Fl{\"a}chen wie Brachen, Straßenr{\"a}ndern, Lagerpl{\"a}tzen, Weinbergr{\"a}ndern und kann sich mit 1-2 m j{\"a}hrlichem Zuwachs (Satellitenbildauswertung, Vermessungen vor Ort) schnell ausbreiten. Die bekannt gewordenen Fundstellen erstrecken sich vom n{\"o}rdlichen Baden-W{\"u}rttemberg bis in den n{\"o}rdlichsten Teil von Bayern (Rh{\"o}n).},
  subject      = {Brombeere},
  language  = {de}
}
@article{BiermannHeilmannDidieetal.2012,
  author    = {Biermann, Daniel and Heilmann, Andreas and Didi{\´e}, Michael and Schlossarek, Saskia and Wahab, Azadeh and Grimm, Michael and R{\"o}mer, Maria and Reichenspurner, Hermann and Sultan, Karim R. and Steenpass, Anna and Erg{\"u}n, S{\"u}leyman and Donzelli, Sonia and Carrier, Lucie and Ehmke, Heimo and Zimmermann, Wolfram H. and Hein, Lutz and B{\"o}ger, Rainer H. and Benndorf, Ralf A.},
  title     = {Impact of AT2 Receptor Deficiency on Postnatal Cardiovascular Development},
  series = {PLoS One},
  volume    = {7},
  journal   = {PLoS One},
  number    = {10},
  doi       = {10.1371/journal.pone.0047916},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-134902},
  pages     = {e47916},
  year      = {2012},
  abstract  = {Background: The angiotensin II receptor subtype 2 (AT2 receptor) is ubiquitously and highly expressed in early postnatal life. However, its role in postnatal cardiac development remained unclear. Methodology/Principal Findings: Hearts from 1, 7, 14 and 56 days old wild-type (WT) and AT2 receptor-deficient (KO) mice were extracted for histomorphometrical analysis as well as analysis of cardiac signaling and gene expression. Furthermore, heart and body weights of examined animals were recorded and echocardiographic analysis of cardiac function as well as telemetric blood pressure measurements were performed. Moreover, gene expression, sarcomere shortening and calcium transients were examined in ventricular cardiomyocytes isolated from both genotypes. KO mice exhibited an accelerated body weight gain and a reduced heart to body weight ratio as compared to WT mice in the postnatal period. However, in adult KO mice the heart to body weight ratio was significantly increased most likely due to elevated systemic blood pressure. At postnatal day 7 ventricular capillarization index and the density of \(\alpha\)-smooth muscle cell actin-positive blood vessels were higher in KO mice as compared to WT mice but normalized during adolescence. Echocardiographic assessment of cardiac systolic function at postnatal day 7 revealed decreased contractility of KO hearts in response to beta-adrenergic stimulation. Moreover, cardiomyocytes from KO mice showed a decreased sarcomere shortening and an increased peak Ca\(^{2+}\) transient in response to isoprenaline when stimulated concomitantly with angiotensin II. Conclusion: The AT2 receptor affects postnatal cardiac growth possibly via reducing body weight gain and systemic blood pressure. Moreover, it moderately attenuates postnatal vascularization of the heart and modulates the beta adrenergic response of the neonatal heart. These AT2 receptor-mediated effects may be implicated in the physiological maturation process of the heart.},
  language  = {en}
}
@article{DrenckhahnBaumgartnerZonneveld2017,
  author    = {Drenckhahn, Detlev and Baumgartner, Werner and Zonneveld, Ben},
  title     = {Different genome sizes of Western and Eastern Ficaria verna lineages shed light on steps of Ficaria evolution},
  series = {Forum Geobotanicum},
  volume    = {7},
  journal   = {Forum Geobotanicum},
  issn      = {1867-9315},
  doi       = {10.3264/FG.2017.1122},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-155061},
  pages     = {27-33},
  year      = {2017},
  abstract  = {The genus Ficaria is now considered to comprize eight Eurasian species. The most widespread European species is the tetraploid F. verna Huds. The present study provides evidence for the existence of two main lineages of F. verna that differ considerably in their genomic size by about 3 pg. A Western F. verna lineage west of river Rhine displays a mean genome size (2C-value) of 34.2 pg and is almost precisely codistributed with the diploid F. ambigua Boreau (20 pg) north of the Mediterranean. The remaining part of Europe appears to be occupied by the Eastern F. verna lineage solely (mean genome size of 31.3 pg) which codistributes in South-Eastern Europe with the diploid F. calthifolia Rchb. (15 pg). There is little overlap at the boundary of Western and Eastern F. verna lineages with the occurrence of a separate intermediate group in the Netherlands (mean genomic size of 33.2 pg) that appears to result from hybridization of both lineages. On the basis of these observations and further considerations we propose development of F. ambigua and F. calthifolia south of the Alps with subsequent divergence to populate their current Western and Eastern European ranges, respectively. The Western F. verna lineage is proposed to originate from autotetraploidization of F. ambigua (precursor) with moderate genomic downsizing and the Eastern F. verna lineage from auto¬tetraploidization of F. calthifolia (precursor).},
  subject      = {Durchflusscytometrie},
  language  = {en}
}
@article{ThangarajSelvarajFrankBenderetal.2012,
  author    = {Thangaraj Selvaraj, Bhuvaneish and Frank, Nicolas and Bender, Florian L. P. and Asan, Esther and Sendtner, Michael},
  title     = {Local axonal function of STAT3 rescues axon degeneration in the pmn model of motoneuron disease},
  series = {The Journal of Cell Biology},
  volume    = {199},
  journal   = {The Journal of Cell Biology},
  number    = {3},
  doi       = {10.1083/jcb.201203109},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-154675},
  pages     = {437 -- 451},
  year      = {2012},
  abstract  = {Axonal maintenance, plasticity, and regeneration are influenced by signals from neighboring cells, in particular Schwann cells of the peripheral nervous system. Schwann cells produce neurotrophic factors, but the mechanisms by which ciliary neurotrophic factor (CNTF) and other neurotrophic molecules modify the axonal cytoskeleton are not well understood. In this paper, we show that activated signal transducer and activator of transcription-3 (STAT3), an intracellular mediator of the effects of CNTF and other neurotrophic cytokines, acts locally in axons of motoneurons to modify the tubulin cytoskeleton. Specifically, we show that activated STAT3 interacted with stathmin and inhibited its microtubule-destabilizing activity. Thus, ectopic CNTF-mediated activation of STAT3 restored axon elongation and maintenance in motoneurons from progressive motor neuronopathy mutant mice, a mouse model of motoneuron disease. This mechanism could also be relevant for other neurodegenerative diseases and provide a target for new therapies for axonal degeneration.},
  language  = {en}
}
@article{WunschZhangHansonetal.2015,
  author    = {Wunsch, Marie and Zhang, Wenji and Hanson, Jodi and Caspell, Richard and Karulin, Alexey Y. and Recks, Mascha S. and Kuerten, Stefanie and Sundararaman, Srividya and Lehmann, Paul V.},
  title     = {Characterization of the HCMV-Specific CD4 T Cell Responses that Are Associated with Protective Immunity},
  series = {Viruses},
  volume    = {7},
  journal   = {Viruses},
  doi       = {10.3390/v7082828},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-151462},
  pages     = {4414 -- 4437},
  year      = {2015},
  abstract  = {Most humans become infected with human cytomegalovirus (HCMV). Typically, the immune system controls the infection, but the virus persists and can reactivate in states of immunodeficiency. While substantial information is available on the contribution of CD8 T cells and antibodies to anti-HCMV immunity, studies of the T\(_{H}\)1, T\(_{H}\)2, and T\(_{H}\)17 subsets have been limited by the low frequency of HCMV-specific CD4 T cells in peripheral blood mononuclear cell (PBMC). Using the enzyme-linked Immunospot\(^{®}\) assay (ELISPOT) that excels in low frequency measurements, we have established these in a sizable cohort of healthy HCMV controllers. Cytokine recall responses were seen in all seropositive donors. Specifically, interferon (IFN)-\({\gamma}\) and/or interleukin (IL)-17 were seen in isolation or with IL-4 in all test subjects. IL-4 recall did not occur in isolation. While the ratios of T\(_{H}\)1, T\(_{H}\)2, and T\(_{H}\)17 cells exhibited substantial variations between different individuals these ratios and the frequencies were relatively stable when tested in samples drawn up to five years apart. IFN-\({\gamma}\) and IL-2 co-expressing polyfunctional cells were seen in most subjects. Around half of the HCMV-specific CD4 cells were in a reversible state of exhaustion. The data provided here established the T\(_{H}\)1, T\(_{H}\)2, and T\(_{H}\)17 characteristic of the CD4 cells that convey immune protection for successful immune surveillance against which reactivity can be compared when the immune surveillance of HCMV fails.},
  language  = {en}
}
@phdthesis{Schampel2017,
  author    = {Schampel, Andrea},
  title     = {Beneficial therapeutic effects of the L-type calcium channel antagonist nimodipine in experimental autoimmune encephalomyelitis - an animal model for multiple sclerosis},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-148952},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2017},
  abstract  = {Multiple sclerosis (MS) is the most prevalent neurological disease of the central nervous system (CNS) in young adults and is characterized by inflammation, demyelination and axonal pathology that result in multiple neurological and cognitive deficits. The focus of MS research remains on modulating the immune response, but common therapeutic strategies are only effective in slowing down disease progression and attenuating the symptoms; they cannot cure the disease. Developing an option to prevent neurodegeneration early on would be a valuable addition to the current standard of care for MS. Based on our results we suggest that application of nimodipine could be an effective way to target both neuroinflammation and neurodegeneration. We performed detailed analyses of neurodegeneration in experimental autoimmune encephalomyelitis (EAE), an animal model of MS, and in in vitro experiments regarding the effect of the clinically well-established L-type calcium channel antagonist nimodipine. Nimodipine treatment attenuated the course of EAE and spinal cord histopathology. Furthermore, it promoted remyelination. The latter could be due to the protective effect on oligodendrocytes and oligodendrocyte precursor cells (OPCs) we observed in response to nimodipine treatment. To our surprise, we detected calcium channel-independent effects on microglia, resulting in apoptosis. These effects were cell type-specific and independent of microglia polarization. Apoptosis was accompanied by decreased levels of nitric oxide (NO) and inducible NO synthase (iNOS) in cell culture as well as decreased iNOS expression and reactive oxygen species (ROS) activity in EAE. Overall, application of nimodipine seems to generate a favorable environment for regenerative processes and could therefore be a novel treatment option for MS, combining immunomodulatory effects while promoting neuroregeneration.},
  subject      = {Nimodipin},
  language  = {en}
}
@article{RovitusoSchefflerWunschetal.2016,
  author    = {Rovituso, Damiano M. and Scheffler, Laura and Wunsch, Marie and Kleinschnitz, Christoph and D{\"o}rck, Sebastian and Ulzheimer, Jochen and Bayas, Antonios and Steinman, Lawrence and Erg{\"u}n, S{\"u}leyman and Kuerten, Stefanie},
  title     = {CEACAM1 mediates B cell aggregation in central nervous system autoimmunity},
  series = {Scientific Reports},
  volume    = {6},
  journal   = {Scientific Reports},
  doi       = {10.1038/srep29847},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-147690},
  pages     = {29847},
  year      = {2016},
  abstract  = {B cell aggregates in the central nervous system (CNS) have been associated with rapid disease progression in patients with multiple sclerosis (MS). Here we demonstrate a key role of carcinoembryogenic antigen-related cell adhesion molecule1 (CEACAM1) in B cell aggregate formation in MS patients and a B cell-dependent mouse model of MS. CEACAM1 expression was increased on peripheral blood B cells and CEACAM1\(^+\) B cells were present in brain infiltrates of MS patients. Administration of the anti-CEACAM1 antibody T84.1 was efficient in blocking aggregation of B cells derived from MS patients. Along these lines, application of the monoclonal anti-CEACAM1 antibody mCC1 was able to inhibit CNS B cell aggregate formation and significantly attenuated established MS-like disease in mice in the absence of any adverse effects. CEACAM1 was co-expressed with the regulator molecule T cell immunoglobulin and mucin domain -3 (TIM-3) on B cells, a novel molecule that has recently been described to induce anergy in T cells. Interestingly, elevated coexpression on B cells coincided with an autoreactive T helper cell phenotype in MS patients. Overall, these data identify CEACAM1 as a clinically highly interesting target in MS pathogenesis and open new therapeutic avenues for the treatment of the disease.},
  language  = {en}
}
@article{WunschHohmannMillesetal.2016,
  author    = {Wunsch, Marie and Hohmann, Christopher and Milles, Bianca and Rostermund, Christina and Lehmann, Paul V. and Schroeter, Michael and Bayas, Antonios and Ulzheimer, Jochen and M{\"a}urer, Mathias and Erg{\"u}n, S{\"u}leyman and Kuerten, Stefanie},
  title     = {The Correlation between the Virus- and Brain Antigen-Specific B Cell Response in the Blood of Patients with Multiple Sclerosis},
  series = {Viruses},
  volume    = {8},
  journal   = {Viruses},
  number    = {4},
  doi       = {10.3390/v8040105},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-146946},
  pages     = {105},
  year      = {2016},
  abstract  = {There is a largely divergent body of literature regarding the relationship between Epstein-Barr virus (EBV) infection and brain inflammation in multiple sclerosis (MS). Here, we tested MS patients during relapse (n = 11) and in remission (n = 19) in addition to n = 22 healthy controls to study the correlation between the EBV- and brain-specific B cell response in the blood by enzyme-linked immunospot (ELISPOT) and enzyme-linked immunosorbent assay (ELISA). Cytomegalovirus (CMV) was used as a control antigen tested in n = 16 MS patients during relapse and in n = 35 patients in remission. Over the course of the study, n = 16 patients were untreated, while n = 33 patients received immunomodulatory therapy. The data show that there was a moderate correlation between the frequencies of EBV- and brain-reactive B cells in MS patients in remission. In addition we could detect a correlation between the B cell response to EBV and disease activity. There was no evidence of an EBV reactivation. Interestingly, there was also a correlation between the frequencies of CMV- and brain-specific B cells in MS patients experiencing an acute relapse and an elevated B cell response to CMV was associated with higher disease activity. The trend remained when excluding seronegative subjects but was non-significant. These data underline that viral infections might impact the immunopathology of MS, but the exact link between the two entities remains subject of controversy.},
  language  = {en}
}
@article{PrinzKaraciviStormannsetal.2015,
  author    = {Prinz, Johanna and Karacivi, Aylin and Stormanns, Eva R. and Recks, Masha S. and K{\"u}rten, Stefanie},
  title     = {Time-Dependent Progression of Demyelination and Axonal Pathology in MP4-Induced Experimental Autoimmune Encephalomyelitis},
  series = {PloS One},
  volume    = {10},
  journal   = {PloS One},
  number    = {12},
  doi       = {10.1371/journal.pone.0144847},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-146651},
  pages     = {e0144847},
  year      = {2015},
  abstract  = {Background Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) characterized by inflammation, demyelination and axonal pathology. Myelin basic protein/proteolipid protein (MBP-PLP) fusion protein MP4 is capable of inducing chronic experimental autoimmune encephalomyelitis (EAE) in susceptible mouse strains mirroring diverse histopathological and immunological hallmarks of MS. Limited availability of human tissue underscores the importance of animal models to study the pathology of MS. Methods Twenty-two female C57BL/6 (B6) mice were immunized with MP4 and the clinical development of experimental autoimmune encephalomyelitis (EAE) was observed. Methylene blue-stained semi-thin and ultra-thin sections of the lumbar spinal cord were assessed at the peak of acute EAE, three months (chronic EAE) and six months after onset of EAE (long-term EAE). The extent of lesional area and inflammation were analyzed in semi-thin sections on a light microscopic level. The magnitude of demyelination and axonal damage were determined using electron microscopy. Emphasis was put on the ventrolateral tract (VLT) of the spinal cord. Results B6 mice demonstrated increasing demyelination and severe axonal pathology in the course of MP4-induced EAE. In addition, mitochondrial swelling and a decrease in the nearest neighbor neurofilament distance (NNND) as early signs of axonal damage were evident with the onset of EAE. In semi-thin sections we observed the maximum of lesional area in the chronic state of EAE while inflammation was found to a similar extent in acute and chronic EAE. In contrast to the well-established myelin oligodendrocyte glycoprotein (MOG) model, disease stages of MP4-induced EAE could not be distinguished by assessing the extent of parenchymal edema or the grade of inflammation. Conclusions Our results complement our previous ultrastructural studies of B6 EAE models and suggest that B6 mice immunized with different antigens constitute useful instruments to study the diverse histopathological aspects of MS.},
  language  = {en}
}