@article{HaertleinSchiesslWagneretal.1983,
  author    = {H{\"a}rtlein, Michael and Schiessl, Sigrid and Wagner, Wilma and Rdest, Ursula and Kreft, J{\"u}rgen and Goebel, Werner},
  title     = {Transport of hemolysin by Escherichia coli},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-60619},
  year      = {1983},
  abstract  = {No abstract available},
  subject      = {Biologie},
  language  = {en}
}
@article{BinderMayBaronetal.2011,
  author    = {Binder, Andreas and May, Denisa and Baron, Ralf and Maier, Christoph and T{\"o}lle, Thomas R. and Treede, Rolf-Detlef and Berthele, Achim and Faltraco, Frank and Flor, Herta and Gierthm{\"u}hlen, Janne and Haenisch, Sierk and Huge, Volker and Magerl, Walter and Maih{\"o}fner, Christian and Richter, Helmut and Rolke, Roman and Scherens, Andrea and {\"U}{\c{c}}eyler, Nurcan and Ufer, Mike and Wasner, Gunnar and Zhu, Jihong and Cascorbi, Ingolf},
  title     = {Transient Receptor Potential Channel Polymorphisms Are Associated with the Somatosensory Function in Neuropathic Pain Patients},
  series = {PLoS ONE},
  volume    = {6},
  journal   = {PLoS ONE},
  number    = {3},
  doi       = {10.1371/journal.pone.0017387},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-142782},
  pages     = {e17387},
  year      = {2011},
  abstract  = {Transient receptor potential channels are important mediators of thermal and mechanical stimuli and play an important role in neuropathic pain. The contribution of hereditary variants in the genes of transient receptor potential channels to neuropathic pain is unknown. We investigated the frequency of transient receptor potential ankyrin 1, transient receptor potential melastin 8 and transient receptor potential vanilloid 1 single nucleotide polymorphisms and their impact on somatosensory abnormalities in neuropathic pain patients. Within the German Research Network on Neuropathic Pain (Deutscher Forscbungsverbund Neuropathischer Schmerz) 371 neuropathic pain patients were phenotypically characterized using standardized quantitative sensory testing. Pyrosequencing was employed to determine a total of eleven single nucleotide polymorphisms in transient receptor potential channel genes of the neuropathic pain patients and a cohort of 253 German healthy volunteers. Associations of quantitative sensory testing parameters and single nucleotide polymorphisms between and within groups and subgroups, based on sensory phenotypes, were analyzed. Single nucleotide polymorphisms frequencies did not differ between both the cohorts. However, in neuropathic pain patients transient receptor potential ankyrin 1 710G>A (rs920829, E179K) was associated with the presence of paradoxical heat sensation (p=0.03), and transient receptor potential vanilloid 1 1911A>G (rs8065080, I585V) with cold hypoalgesia (p=0.0035). Two main subgroups characterized by preserved (1) and impaired (2) sensory function were identified. In subgroup 1 transient receptor potential vanilloid 1 1911A>G led to significantly less heat hyperalgesia, pinprick hyperalgesia and mechanical hypaesthesia (p=0.006, p=0.005 and p<0.001) and transient receptor potential vanilloid 1 1103C>G (rs222747, M315I) to cold hypaesthesia (p=0.002), but there was absence of associations in subgroup 2. In this study we found no evidence that genetic variants of transient receptor potential channels are involved in the expression of neuropathic pain, but transient receptor potential channel polymorphisms contributed significantly to the somatosensory abnormalities of neuropathic pain patients.},
  language  = {en}
}
@article{RauertStuehmerBargouetal.2011,
  author    = {Rauert, H. and St{\"u}hmer, T. and Bargou, R. and Wajant, H. and Siegmund, D.},
  title     = {TNFR1 and TNFR2 regulate the extrinsic apoptotic pathway in myeloma cells by multiple mechanisms},
  series = {Cell Death and Disease},
  volume    = {2},
  journal   = {Cell Death and Disease},
  doi       = {10.1038/cddis.2011.78},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-133486},
  pages     = {e194},
  year      = {2011},
  abstract  = {The huge majority of myeloma cell lines express TNFR2 while a substantial subset of them failed to show TNFR1 expression. Stimulation of TNFR1 in the TNFR1-expressing subset of MM cell lines had no or only a very mild effect on cellular viability. Surprisingly, however, TNF stimulation enhanced cell death induction by CD95L and attenuated the apoptotic effect of TRAIL. The contrasting regulation of TRAIL- and CD95L-induced cell death by TNF could be traced back to the concomitant NFjBmediated upregulation of CD95 and the antiapoptotic FLIP protein. It appeared that CD95 induction, due to its strength, overcompensated a rather moderate upregulation of FLIP so that the net effect of TNF-induced NFjB activation in the context of CD95 signaling is pro-apoptotic. TRAIL-induced cell death, however, was antagonized in response to TNF because in this context only the induction of FLIP is relevant. Stimulation of TNFR2 in myeloma cells leads to TRAF2 depletion. In line with this, we observed cell death induction in TNFR1-TNFR2-costimulated JJN3 cells. Our studies revealed that the TNF-TNF receptor system adjusts the responsiveness of the extrinsic apoptotic pathway in myeloma cells by multiple mechanisms that generate a highly context-dependent net effect on myeloma cell survival},
  language  = {en}
}
@phdthesis{Kreutzfeldt2013,
  author    = {Kreutzfeldt, Simon},
  title     = {Studien zur Expression von Megalencephalic leukoencephalopathy with subcortical cysts 1 (MLC1/Mlc1) in humanen und murinen Geweben},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-90355},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2013},
  abstract  = {Das humane MLC1 (auch als KIAA0027 oder WKL1 benannt) ist ein 377 AS umfassendes Protein, welches vornehmlich in neuralen Geweben exprimiert wird. Aufgrund von Strukturanalysen und Homologievergleichen wurde eine Funktion als Ionenkanal mit acht Transmembrandom{\"a}nen postuliert. Loss-of-function-Mutationen des MLC1-Gens lassen sich mit dem Auftreten der Megalenzephale Leukenzephalopathie mit subkortikalen Zysten korrelieren. Ferner konnte anhand einer Stammbaumanalyse gezeigt werden, dass die C1121A-Mutation in einer gr{\"o}ßeren Familie mit dem Auftreten der Periodischen Katatonie nach Leonhardt (PK) kosegregierte, wobei Folgeuntersuchungen zur Assoziation von MLC1-Mutationen und dem Auftreten der PK widerspr{\"u}chliche Ergebnisse erbrachten. Zur weiteren Aufkl{\"a}rung der biologischen Funktion von MLC1 war es das Ziel der vorliegenden Arbeit, in zwei experimentellen Ans{\"a}tzen n{\"a}here Kenntnisse zum transkriptionellen Expressionsmuster von MLC1 in vivo zu gewinnen, und anschließend durch Herstellung eines polyklonalen Antik{\"o}rpers gegen das humane MLC1 den Grundstein f{\"u}r weitergehende Untersuchungen zur funktionellen Bedeutung von MLC1 zu legen. Mittels In Situ-Hybridisierung humaner und muriner Gewebeschnitte aus Hippocampus und Cerebellum konnte gezeigt werden, dass die MLC1/Mlc1-Transkription in diesen Geweben vornehmlich in den Bergmann-Gliazellen der Purkinjezellschicht des Cerebellums sowie - in schw{\"a}cherem Umfang - in verstreut liegenden und in der subgranul{\"a}ren Zone des Gyrus dentatus geh{\"a}uften Astrozyten des murinen Hippocampus nachweisbar war. Im zweiten Schritt der Analyse wurden humane post-mortem cDNA-Proben aus verschiedenen Gehirnregionen und zus{\"a}tzlich einigen nicht-neuralen Geweben von zwei Menschen gewonnen, mittels quantitativer Real-time-PCR die Genexpression von MLC1 bestimmt und mithilfe des Expressionsniveaus von ausgew{\"a}hlten Housekeeping-Genen (GAPDH, L13a, β-Aktin, ARP und Cyclophilin) normalisiert. Es zeigte sich, dass in allen getesteten Hirnregionen eine deutliche MLC1-Expression festzustellen war, deren Maxima im Cerebellum und Frontalhirn und deren Minima im Putamen bzw. im nicht-neuralen Plexus chorioideus lagen. Zudem konnte eine nicht-neurale Expression auf sehr geringem Niveau f{\"u}r Lunge und Milz nachgewiesen werden. Zur Gewinnung eines polyklonalen Antik{\"o}rpers gegen humanes MLC1 wurden mittels computergest{\"u}tzter Verfahren ein 117 AS langes Vakzinierungsprotein entworfen, welches immunogene Abschnitte des N-Terminus (61 AS) und C-Terminus (54 AS) enthielt. Die kodierende Sequenz wurde unter Verwendung des Impact-CN®-Expressionssystems in einen pTYB-Vektor kloniert, in ER2566-Zellen exprimiert, das Protein affinit{\"a}tschromatographisch {\"u}ber Chitin-S{\"a}ulen isoliert und aufgereinigt und mittels Bradford-Assay und SDS-Gelelektrophorese nachgewiesen. Leider konnte trotz vielf{\"a}ltiger Variation der Versuchsparameter kein eindeutiger Nachweis einer ausreichenden Expression des MLC1-Proteins in den ER2566-Zellen erbracht werden, die f{\"u}r die anschließende Vakzinierung von Kaninchen zur Gewinnung des polyklonalen Antiserums erforderlich gewesen w{\"a}re. Die Gr{\"u}nde hierf{\"u}r sind unklar, denkbar sind beispielsweise eine suboptimale Codon-Frequenz, eine schlechte Proteinl{\"o}slichkeit, intrazellul{\"a}re mRNA-Degradation, proteolytische Abbauvorg{\"a}nge oder eine Hemmung der Proteinbiosynthese durch die biologische Funktion des Proteins. Zusammenfassend konnten die im Rahmen dieser Arbeit erzielten Ergebnisse einen Beitrag zur Erweiterung des Wissens zur MLC1-Expression leisten. Dabei entsprachen die Befunde zur humanen MLC1-Expression weitgehend den diesbez{\"u}glichen Beobachtungen zur regionalen und zellul{\"a}ren Expressionsst{\"a}rkenverteilung aus dem Mausmodell, welche eine funktionelle Bedeutung von MLC1 im Rahmen von neuralen Schrankenstrukturen nahelegten (vgl. Schmitt et al. 2003). Mittels der zwischenzeitlich von anderen Arbeitsgruppen ({\"u}ber andere experimentelle Verfahren) erzeugten Antik{\"o}rper gegen MLC1 konnte gezeigt werden, dass funktionelles MLC1 vermutlich als zellmembranst{\"a}ndiges Dimer vorliegt und seine biologische Funktion u.a. durch Interaktion mit dem DGC (=Dystrophin-assoziierten Glykoprotein-Komplex) in den Caveolae aus{\"u}bt. Es bleibt eine Aufgabe f{\"u}r die Zukunft, die genauen molekularen Mechanismen dieser Prozesse und ihre m{\"o}gliche therapeutische Beeinflussbarkeit zur Behandlung der MLC zu erforschen. Auch die Frage der potenziellen extraneuralen MLC1-Expression, f{\"u}r die in dieser Arbeit Hinweise gefunden wurden, mag ein interessanter Ansatzpunkt f{\"u}r zuk{\"u}nftige Forschungsarbeiten sein.},
  subject      = {MLC1},
  language  = {de}
}
@article{BergmillerPenaMillerBoehmetal.2011,
  author    = {Bergmiller, Tobias and Pena-Miller, Rafael and Boehm, Alexander and Ackermann, Martin},
  title     = {Single-cell time-lapse analysis of depletion of the universally conserved essential protein YgjD},
  series = {BMC Microbiology},
  volume    = {11},
  journal   = {BMC Microbiology},
  number    = {118},
  doi       = {10.1186/1471-2180-11-118},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-142324},
  pages     = {1-12},
  year      = {2011},
  abstract  = {Background: The essential Escherichia coli gene ygjD belongs to a universally conserved group of genes whose function has been the focus of a number of recent studies. Here, we put ygjD under control of an inducible promoter, and used time-lapse microscopy and single cell analysis to investigate the phenotypic consequences of the depletion of YgjD protein from growing cells. Results: We show that loss of YgjD leads to a marked decrease in cell size and termination of cell division. The transition towards smaller size occurs in a controlled manner: cell elongation and cell division remain coupled, but cell size at division decreases. We also find evidence that depletion of YgjD leads to the synthesis of the intracellular signaling molecule (p) ppGpp, inducing a cellular reaction resembling the stringent response. Concomitant deletion of the relA and spoT genes - leading to a strain that is uncapable of synthesizing (p) ppGpp abrogates the decrease in cell size, but does not prevent termination of cell division upon YgjD depletion. Conclusions: Depletion of YgjD protein from growing cells leads to a decrease in cell size that is contingent on (p) ppGpp, and to a termination of cell division. The combination of single-cell time-lapse microscopy and statistical analysis can give detailed insights into the phenotypic consequences of the loss of essential genes, and can thus serve as a new tool to study the function of essential genes.},
  language  = {en}
}
@article{ReinholdSchwabeLuxetal.2018,
  author    = {Reinhold, Ann Kristin and Schwabe, Joachim and Lux, Thomas J. and Salvador, Ellaine and Rittner, Heike L.},
  title     = {Quantitative and Microstructural Changes of the Blood-Nerve Barrier in Peripheral Neuropathy},
  series = {Frontiers in Neuroscience},
  volume    = {12},
  journal   = {Frontiers in Neuroscience},
  doi       = {10.3389/fnins.2018.00936},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-225179},
  pages     = {936, 1-9},
  year      = {2018},
  abstract  = {Peripheral neuropathy is accompanied by changes in the neuronal environment. The blood-nerve barrier (BNB) is crucial in protecting the neural homeostasis: Tight junctions (TJ) seal paracellular spaces and thus prevent external stimuli from entering. In different models of neuropathic pain, the BNB is impaired, thus contributing to local damage, immune cell invasion and, ultimately, the development of neuropathy with its symptoms. In this study, we examined changes in expression and microstructural localization of two key tight junction proteins (TJP), claudin-1 and the cytoplasmic anchoring ZO-1, in the sciatic nerve of mice subjected to chronic constriction injury (CCI). Via qPCR and analysis of fluorescence immunohistochemistry, a marked downregulation of mRNA as well as decreased fluorescence intensity were observed in the nerve for both proteins. Moreover, a distinct zig-zag structure for both proteins located at cell-cell contacts, indicative of the localization of TJs, was observed in the perineurial compartment of sham-operated animals. This microstructural location in cell-cell-contacts was lost in neuropathy as semiquantified via computational analysis, based on a novel algorithm. In summary, we provide evidence that peripheral neuropathy is not only associated with decrease in relevant TJPs but also exhibits alterations in TJP arrangement and loss in barrier tightness, presumably due to internalization. Specifically, semiquantification of TJP in cell-cell-contacts of microcompartments could be used in the future for routine clinical samples of patients with neuropathy.},
  language  = {en}
}
@phdthesis{Rauthe2008,
  author    = {Rauthe, Stephan Christian},
  title     = {Nachweis von Blimp-1 mRNA und Protein in humanen T-Zell-Subpopulationen},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-28056},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2008},
  abstract  = {Der transkriptionelle Repressor Blimp-1 wurde urspr{\"u}nglich als essentiell f{\"u}r die terminale Differenzierung von B-Zellen zu Antik{\"o}rper-produzierenden Plasmazellen beschrieben. Im Rahmen dieser Arbeit wurde die Expression von Blimp-1 in humanen T-Zellen untersucht. Die Versuchsergebnisse zeigen, dass Blimp-1 auch in humanen T-Zellen sowohl auf mRNA- als auch auf Proteinebene exprimiert wird. Es ist deshalb anzunehmen, dass Blimp-1 auch f{\"u}r die terminale Differenzierung von T-Zellen eine wichtige Rolle spie},
  subject      = {Expression},
  language  = {de}
}
@article{YinBrocherFischeretal.2011,
  author    = {Yin, Jun and Brocher, Jan and Fischer, Utz and Winkler, Christoph},
  title     = {Mutant Prpf31 causes pre-mRNA splicing defects and rod photoreceptor cell degeneration in a zebrafish model for Retinitis pigmentosa},
  series = {Molecular neurodegeneration},
  volume    = {6},
  journal   = {Molecular neurodegeneration},
  number    = {56},
  doi       = {10.1186/1750-1326-6-56},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-141090},
  pages     = {1-17},
  year      = {2011},
  abstract  = {Background: Retinitis pigmentosa (RP) is an inherited eye disease characterized by the progressive degeneration of rod photoreceptor cells. Mutations in pre-mRNA splicing factors including PRPF31 have been identified as cause for RP, raising the question how mutations in general factors lead to tissue specific defects. Results: We have recently shown that the zebrafish serves as an excellent model allowing the recapitulation of key events of RP. Here we use this model to investigate two pathogenic mutations in PRPF31, SP117 and AD5, causing the autosomal dominant form of RP. We show that SP117 leads to an unstable protein that is mislocalized to the rod cytoplasm. Importantly, its overexpression does not result in photoreceptor degeneration suggesting haploinsufficiency as the underlying cause in human RP patients carrying SP117. In contrast, overexpression of AD5 results in embryonic lethality, which can be rescued by wild-type Prpf31. Transgenic retina-specific expression of AD5 reveals that stable AD5 protein is initially localized in the nucleus but later found in the cytoplasm concurrent with progressing rod outer segment degeneration and apoptosis. Importantly, we show for the first time in vivo that retinal transcripts are wrongly spliced in adult transgenic retinas expressing AD5 and exhibiting increased apoptosis in rod photoreceptors. Conclusion: Our data suggest that distinct mutations in Prpf31 can lead to photoreceptor degeneration through different mechanisms, by haploinsufficiency or dominant-negative effects. Analyzing the AD5 effects in our animal model in vivo, our data imply that aberrant splicing of distinct retinal transcripts contributes to the observed retina defects.},
  language  = {en}
}
@article{WedelHudakSeibeletal.2011,
  author    = {Wedel, Steffen and Hudak, Lukasz and Seibel, Jens-Michael and Makarevic, Jasmina and Juengel, Eva and Tsaur, Igor and Waaga-Gasser, Ana and Haferkamp, Axel and Blaheta, Roman A.},
  title     = {Molecular targeting of prostate cancer cells by a triple drug combination down-regulates integrin driven adhesion processes, delays cell cycle progression and interferes with the cdk-cyclin axis},
  series = {BMC Cancer},
  volume    = {11},
  journal   = {BMC Cancer},
  number    = {375},
  doi       = {10.1186/1471-2407-11-375},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-141075},
  pages     = {1-14},
  year      = {2011},
  abstract  = {Background: Single drug use has not achieved satisfactory results in the treatment of prostate cancer, despite application of increasingly widespread targeted therapeutics. In the present study, the combined impact of the mammalian target of rapamycin (mTOR)-inhibitor RAD001, the dual EGFr and VGEFr tyrosine kinase inhibitor AEE788 and the histone deacetylase (HDAC)-inhibitor valproic acid (VPA) on prostate cancer growth and adhesion in vitro was investigated. Methods: PC-3, DU-145 and LNCaP cells were treated with RAD001, AEE788 or VPA or with a RAD-AEE-VPA combination. Tumor cell growth, cell cycle progression and cell cycle regulating proteins were then investigated by MTT-assay, flow cytometry and western blotting, respectively. Furthermore, tumor cell adhesion to vascular endothelium or to immobilized extracellular matrix proteins as well as migratory properties of the cells was evaluated, and integrin alpha and beta subtypes were analyzed. Finally, effects of drug treatment on cell signaling pathways were determined. Results: All drugs, separately applied, reduced tumor cell adhesion, migration and growth. A much stronger anticancer effect was evoked by the triple drug combination. Particularly, cdk1, 2 and 4 and cyclin B were reduced, whereas p27 was elevated. In addition, simultaneous application of RAD001, AEE788 and VPA altered the membranous, cytoplasmic and gene expression pattern of various integrin alpha and beta subtypes, reduced integrin-linked kinase (ILK) and deactivated focal adhesion kinase (FAK). Signaling analysis revealed that EGFr and the downstream target Akt, as well as p70S6k was distinctly modified in the presence of the drug combination. Conclusions: Simultaneous targeting of several key proteins in prostate cancer cells provides an advantage over targeting a single pathway. Since strong anti-tumor properties became evident with respect to cell growth and adhesion dynamics, the triple drug combination might provide progress in the treatment of advanced prostate cancer.},
  language  = {en}
}
@article{SailerWiedemannStraussetal.2019,
  author    = {Sailer, Clara Odilia and Wiedemann, Sophia Julia and Strauss, Konrad and Schnyder, Ingeborg and Fenske, Wiebke Kristin and Christ-Crain, Mirjam},
  title     = {Markers of systemic inflammation in response to osmotic stimulus in healthy volunteers},
  series = {Endocrine Connections},
  volume    = {8},
  journal   = {Endocrine Connections},
  number    = {9},
  doi       = {10.1530/EC-19-0280},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-227204},
  pages     = {1282-1287},
  year      = {2019},
  abstract  = {Osmotic stimulus or stress results in vasopressin release. Animal and human in vitro studies have shown that inflammatory parameters, such as interle ukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-alpha), increase in parallel in the central nervous system and bronchial, corneal or intestinal epithelial cell lines in response to osmotic stimulus. Whether osmotic stimulus directly causes a systemic inflammatory response in humans is unknown. We therefore investigated the influence of osmotic stimulus on circulatory markers of systemic inflammation in healthy volunteers. In this prospective cohort study, 44 healthy volunteers underwent a standardized test protocol with an osmotic stimulus leading into the hyperosmotic/hypernatremic range (serum sodium >= 150 mmol/L) by hypertonic saline infusion. Copeptin - a marker indicating vasopressin activity - serum sodium and osmolality, plasma IL-8 and TNF-alpha were measured at baseline and directly after osmotic stimulus. Median (range) serum sodium increased from 141 mmol/L (136, 147) to 151 mmol/L (145, 154) (P < 0.01), serum osmolality increased from 295 mmol/L (281, 306) to 315 mmol/L (304, 325) (P < 0.01). Median (range) copeptin increased from 4.3 pg/L (1.1, 21.4) to 28.8 pg/L (19.9, 43.4) (P < 0.01). Median (range) IL-8 levels showed a trend to decrease from 0.79 pg/mL (0.37, 1.6) to 0.7 pg/mL (0.4, 1.9) (P < 0.09) and TNF-alpha levels decreased from 0.53 pg/mL (0.11, 1.1) to 0.45 pg/mL (0.1 2, 0.97) (P < 0.036). Contrary to data obtained in vitro, circulating proinflammatory cytokines tend to or decrease in human plasma after osmotic stimulus. In this study, osmotic stimulus does not increase circulating markers of systemic inflammation.},
  subject      = {Hyperosmotic Stress},
  language  = {en}
}