@article{HansmannHeinzmannWrenzyckietal.2010, author = {Hansmann, T. and Heinzmann, J. and Wrenzycki, C. and Zechner, U. and Niemann, H. and Haaf, T.}, title = {Characterization of Differentially Methylated Regions in 3 Bovine Imprinted Genes: A Model for Studying Human Germ-Cell and Embryo Development}, series = {Cytogenetic and Genome Research}, volume = {132}, journal = {Cytogenetic and Genome Research}, number = {4}, issn = {1424-8581}, doi = {10.1159/000322627}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-199051}, pages = {239-247}, year = {2010}, abstract = {Correct imprinting is crucial for normal fetal and placental development in mammals. Experimental evidence in animal models and epidemiological studies in humans suggest that assisted reproductive technologies (ARTs) can interfere with imprinted gene regulation in gametogenesis and early embryogenesis. Bos taurus is an agriculturally important species in which ARTs are commonly employed. Because this species exhibits a similar preimplantation development and gestation length as humans, it is increasingly being used as a model for human germ-cell and embryo development. However, in contrast to humans and mice, there is relatively little information on bovine imprinted genes. Here, we characterized the bovine intergenic IGF2-H19 imprinting control region (ICR) spanning approximately 3 kb. We identified a 300-bp differentially methylated region (DMR) approximately 6 kb upstream of the H19 promoter, containing a CpG island with CTCF-binding site and high sequence similarity with the human intergenic ICR. Additional differentially methylated CpG islands lie -6 kb to -3 kb upstream of the promoter, however these are less conserved. Both classical bisulfite sequencing and bisulfite pyrosequencing demonstrated complete methylation of the IGF2-H19 ICR in sperm, complete demethylation in parthenogenetic embryos having only the female genome, and differential methylation in placental and somatic tissues. In addition, we established pyrosequencing assays for the previously reported bovine SNRPN and PEG3 DMRs. The observed methylation patterns were consistent with genomic imprinting in all analyzed tissues/cell types. The identified IGF2-H19 ICR and the developed quantitative methylation assays may prove useful for further studies on the relationship between ARTs and imprinting defects in the bovine model.}, language = {en} } @article{StellzigEisenhauerMeyerMarcotty2010, author = {Stellzig-Eisenhauer, Angelika and Meyer-Marcotty, Philipp}, title = {Interaction between otorhinolaryngology and orthodontics: correlation between the nasopharyngeal airway and the craniofacial complex}, series = {GMS Current Topics in Otorhinolaryngology - Head and Neck Surgery}, volume = {9}, journal = {GMS Current Topics in Otorhinolaryngology - Head and Neck Surgery}, number = {Dok04}, doi = {10.3205/cto000068}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-140850}, pages = {1-8}, year = {2010}, abstract = {In terms of pathophysiology, an anatomically narrow airway is a predisposing factor for obstruction of the upper respiratory tract. The correlation between the nasopharyngeal airway and the craniofacial structures is discussed in this context. Thus a mutual interaction between the pharynx and the mandibular position was demonstrated, whereby the transverse dimension of the nasopharynx was significantly larger in patients with prognathism than in patients with retrognathism. The influence of chronic obstruction of the nasal airway on craniofacial development was also discussed. The form-and-function interaction, which ought to explain the causal relationship between nasal obstruction and craniofacial growth, appears to be of a multifactorial rather than a one-dimensional, linear nature. It is not disputed, however, that expanding the maxilla improves not only nasal volume and nasal flow, but also the subjective sensation of patients, although it is not possible to make a prognostic statement about the extent of this improvement because of the differing reactions of individuals. Orthodontic appliances for advancing the mandible can also be successfully used in the treatment of mild obstructive sleep apnea syndrome. This treatment method should be considered particularly for patients who are unwilling to undergo or cannot tolerate CPAP (continuous positive airway pressure) treatment.}, language = {en} } @article{SchneiderPliushchElHajjetal.2010, author = {Schneider, Eberhard and Pliushch, Galyna and El Hajj, Nady and Galetzka, Danuta and Puhl, Alexander and Schorsch, Martin and Frauenknecht, Katrin and Riepert, Thomas and Tresch, Achim and Mueller, Annette M. and Coerdt, Wiltrud and Zechner, Ulrich and Haaf, Thomas}, title = {Spatial, temporal and interindividual epigenetic variation of functionally important DNA methylation patterns}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68371}, year = {2010}, abstract = {DNA methylation is an epigenetic modification that plays an important role in gene regulation. It can be influenced by stochastic events, environmental factors and developmental programs. However, little is known about the natural variation of genespecific methylation patterns. In this study, we performed quantitative methylation analyses of six differentially methylated imprinted genes (H19, MEG3, LIT1, NESP55, PEG3 and SNRPN), one hypermethylated pluripotency gene (OCT4) and one hypomethylated tumor suppressor gene (APC) in chorionic villus, fetal and adult cortex, and adult blood samples. Both average methylation level and range of methylation variation depended on the gene locus, tissue type and/or developmental stage. We found considerable variability of functionally important methylation patterns among unrelated healthy individuals and a trend toward more similar methylation levels in monozygotic twins than in dizygotic twins. Imprinted genes showed relatively little methylation changes associated with aging in individuals who are >25 years. The relative differences in methylation among neighboring CpGs in the generally hypomethylated APC promoter may not only reflect stochastic fluctuations but also depend on the tissue type. Our results are consistent with the view that most methylation variation may arise after fertilization, leading to epigenetic mosaicism.}, subject = {Medizin}, language = {en} } @article{AlbrechtSharmaReinhardtetal.2010, author = {Albrecht, Marco and Sharma, Cynthia M. and Reinhardt, Richard and Vogel, Joerg and Rudel, Thomas}, title = {Deep sequencing-based discovery of the Chlamydia trachomatis transcriptome}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68389}, year = {2010}, abstract = {Chlamydia trachomatis is an obligate intracellular pathogenic bacterium that has been refractory to genetic manipulations. Although the genomes of several strains have been sequenced, very little information is available on the gene structure of these bacteria. We used deep sequencing to define the transcriptome of purified elementary bodies (EB) and reticulate bodies (RB) of C. trachomatis L2b, respectively. Using an RNAseq approach, we have mapped 363 transcriptional start sites (TSS) of annotated genes. Semiquantitative analysis of mapped cDNA reads revealed differences in the RNA levels of 84 genes isolated from EB and RB, respectively. We have identified and in part confirmed 42 genome- and 1 plasmid-derived novel non-coding RNAs. The genome encoded non-coding RNA, ctrR0332 was one of the most abundantly and differentially expressed RNA in EB and RB, implying an important role in the developmental cycle of C. trachomatis. The detailed map of TSS in a thus far unprecedented resolution as a complement to the genome sequence will help to understand the organization, control and function of genes of this important pathogen.}, subject = {Biologie}, language = {en} } @article{KoetschanFoersterKelleretal.2010, author = {Koetschan, Christian and Foerster, Frank and Keller, Alexander and Schleicher, Tina and Ruderisch, Benjamin and Schwarz, Roland and Mueller, Tobias and Wolf, Matthias and Schultz, Joerg}, title = {The ITS2 Database III-sequences and structures for phylogeny}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68390}, year = {2010}, abstract = {The internal transcribed spacer 2 (ITS2) is a widely used phylogenetic marker. In the past, it has mainly been used for species level classifications. Nowadays, a wider applicability becomes apparent. Here, the conserved structure of the RNA molecule plays a vital role. We have developed the ITS2 Database (http://its2.bioapps .biozentrum.uni-wuerzburg.de) which holds information about sequence, structure and taxonomic classification of all ITS2 in GenBank. In the new version, we use Hidden Markov models (HMMs) for the identification and delineation of the ITS2 resulting in a major redesign of the annotation pipeline. This allowed the identification of more than 160 000 correct full ength and more than 50 000 partial structures. In the web interface, these can now be searched with a modified BLAST considering both sequence and structure, enabling rapid taxon sampling. Novel sequences can be annotated using the HMM based approach and modelled according to multiple template structures. Sequences can be searched for known and newly identified motifs. Together, the database and the web server build an exhaustive resource for ITS2 based phylogenetic analyses.}, subject = {Biologie}, language = {en} } @article{LandmannSchrammColditzetal.2010, author = {Landmann, Tobias and Schramm, Matthias and Colditz, Rene R. and Dietz, Andreas and Dech, Stefan}, title = {Wide Area Wetland Mapping in Semi-Arid Africa Using 250-Meter MODIS Metrics and Topographic Variables}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68628}, year = {2010}, abstract = {Wetlands in West Africa are among the most vulnerable ecosystems to climate change. West African wetlands are often freshwater transfer mechanisms from wetter climate regions to dryer areas, providing an array of ecosystem services and functions. Often wetland-specific data in Africa is only available on a per country basis or as point data. Since wetlands are challenging to map, their accuracies are not well considered in global land cover products. In this paper we describe a methodology to map wetlands using well-corrected 250-meter MODIS time-series data for the year 2002 and over a 360,000 km2 large study area in western Burkina Faso and southern Mali (West Africa). A MODIS-based spectral index table is used to map basic wetland morphology classes. The index uses the wet season near infrared (NIR) metrics as a surrogate for flooding, as a function of the dry season chlorophyll activity metrics (as NDVI). Topographic features such as sinks and streamline areas were used to mask areas where wetlands can potentially occur, and minimize spectral confusion. 30-m Landsat trajectories from the same year, over two reference sites, were used for accuracy assessment, which considered the area-proportion of each class mapped in Landsat for every MODIS cell. We were able to map a total of five wetland categories. Aerial extend of all mapped wetlands (class "Wetland") is 9,350 km2, corresponding to 4.3\% of the total study area size. The classes "No wetland"/"Wetland" could be separated with very high certainty; the overall agreement (KHAT) was 84.2\% (0.67) and 97.9\% (0.59) for the two reference sites, respectively. The methodology described herein can be employed to render wide area base line information on wetland distributions in semi-arid West Africa, as a data-scarce region. The results can provide (spatially) interoperable information feeds for inter-zonal as well as local scale water assessments.}, subject = {Geologie}, language = {en} } @article{UeceylerBikoSommer2010, author = {Ueceyler, Nurcan and Biko, Lydia and Sommer, Claudia}, title = {MDL-28170 Has No Analgesic Effect on CCI Induced Neuropathic Pain in Mice}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68359}, year = {2010}, abstract = {The calpain inhibitor MDL-28710 blocks the early local pro-inflammatory cytokine gene expression in mice after chronic constriction nerve injury (CCI). Onehundred- thirteen wild type mice of C57Bl/6J background received CCI of the right sciatic nerve. Mechanical paw withdrawal thresholds and thermal withdrawal latencies were investigated at baseline and at 1, 3, and 7 days after CCI. Three application regimens were used for MDL-28170: a) single injection 40 min before CCI; b) serial injections of MDL- 28170 40 min before and up to day three after CCI; c) sustained application via intraperitoneal osmotic pumps. The control animals received the vehicle DMSO/PEG 400. The tolerable dose of MDL-28170 for mice was 30 mg/kg body weight, higher doses were lethal within the first hours after application. Mechanical withdrawal thresholds and thermal withdrawal latencies were reduced after CCI and did not normalize after single or serial injections, nor with application of MDL-28170 via osmotic pumps. Although the calpain inhibitor MDL-28170 inhibits the early local cytokine upregulation in the sciatic nerve after CCI, pain behavior is not altered. This finding implies that local cytokine upregulation after nerve injury alone is only one factor in the induction and maintenance of neuropathic pain.}, subject = {Medizin}, language = {en} } @article{RotheReinthalerLiuetal.2010, author = {Rothe, D. G. and Reinthaler, R. W. and Liu, C-X and Molenkamp, L. W. and Zhang, S-C and Hankiewicz, E. M.}, title = {Fingerprint of different spin-orbit terms for spin transport in HgTe quantum wells}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68362}, year = {2010}, abstract = {Using k · p theory, we derive an effective four-band model describing the physics of the typical two-dimensional topological insulator (HgTe/CdTe quantum well (QW)) in the presence of an out-of-plane (in the z-direction) inversion breaking potential and an in-plane potential. We find that up to third order in perturbation theory, only the inversion breaking potential generates new elements to the four-band Hamiltonian that are off-diagonal in spin space. When this new effective Hamiltonian is folded into an effective twoband model for the conduction (electron) or valence (heavy hole) bands, two competing terms appear: (i) a Rashba spin-orbit interaction originating from inversion breaking potential in the z-direction and (ii) an in-plane Pauli term as a consequence of the in-plane potential. Spin transport in the conduction band is further analysed within the Landauer-B{\"u}ttiker formalism. We find that for asymmetrically doped HgTe QWs, the behaviour of the spin-Hall conductance is dominated by the Rashba term.}, subject = {Physik}, language = {en} } @article{SchubertUnkmeirKonradSlaninaetal.2010, author = {Schubert-Unkmeir, Alexandra and Konrad, Christian and Slanina, Heiko and Czapek, Florian and Hebling, Sabrina and Frosch, Matthias}, title = {Neisseria meningitidis Induces Brain Microvascular Endothelial Cell Detachment from the Matrix and Cleavage of Occludin: A Role for MMP-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68589}, year = {2010}, abstract = {Disruption of the blood-brain barrier (BBB) is a hallmark event in the pathophysiology of bacterial meningitis. Several inflammatory mediators, such as tumor necrosis factor alpha (TNF-a), nitric oxide and matrix metalloproteinases (MMPs), contribute to this disruption. Here we show that infection of human brain microvascular endothelial cells (HBMEC) with Neisseria meningitidis induced an increase of permeability at prolonged time of infection. This was paralleled by an increase in MMP-8 activity in supernatants collected from infected cells. A detailed analysis revealed that MMP-8 was involved in the proteolytic cleavage of the tight junction protein occludin, resulting in its disappearance from the cell periphery and cleavage to a lower-sized 50-kDa protein in infected HBMEC. Abrogation of MMP-8 activity by specific inhibitors as well as transfection with MMP-8 siRNA abolished production of the cleavage fragment and occludin remained attached to the cell periphery. In addition, MMP-8 affected cell adherence to the underlying matrix. A similar temporal relationship was observed for MMP activity and cell detachment. Injury of the HBMEC monolayer suggested the requirement of direct cell contact because no detachment was observed when bacteria were placed above a transwell membrane or when bacterial supernatant was directly added to cells. Inhibition of MMP-8 partially prevented detachment of infected HBMEC and restored BBB permeability. Together, we established that MMP-8 activity plays a crucial role in disassembly of cell junction components and cell adhesion during meningococcal infection.}, subject = {Neisseria meningitidis}, language = {en} } @article{ZdziarskiBrzuszkiewiczWulltetal.2010, author = {Zdziarski, Jaroslaw and Brzuszkiewicz, Elzbieta and Wullt, Bjorn and Liesegang, Heiko and Biran, Dvora and Voigt, Birgit and Gronberg-Hernandez, Jenny and Ragnarsdottir, Bryndis and Hecker, Michael and Ron, Eliora Z. and Daniel, Rolf and Gottschalk, Gerhard and Hacker, Joerg and Svanborg, Catharina and Dobrindt, Ulrich}, title = {Host Imprints on Bacterial Genomes-Rapid, Divergent Evolution in Individual Patients}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68594}, year = {2010}, abstract = {Bacteria lose or gain genetic material and through selection, new variants become fixed in the population. Here we provide the first, genome-wide example of a single bacterial strain's evolution in different deliberately colonized patients and the surprising insight that hosts appear to personalize their microflora. By first obtaining the complete genome sequence of the prototype asymptomatic bacteriuria strain E. coli 83972 and then resequencing its descendants after therapeutic bladder colonization of different patients, we identified 34 mutations, which affected metabolic and virulence-related genes. Further transcriptome and proteome analysis proved that these genome changes altered bacterial gene expression resulting in unique adaptation patterns in each patient. Our results provide evidence that, in addition to stochastic events, adaptive bacterial evolution is driven by individual host environments. Ongoing loss of gene function supports the hypothesis that evolution towards commensalism rather than virulence is favored during asymptomatic bladder colonization.}, subject = {Proteomanalyse}, language = {en} } @article{WilbertGuckenbergerPolatetal.2010, author = {Wilbert, Juergen and Guckenberger, Matthias and Polat, Buelent and Sauer, Otto and Vogele, Michael and Flentje, Michael and Sweeney, Reinhart A.}, title = {Semi-robotic 6 degree of freedom positioning for intracranial high precision radiotherapy; first phantom and clinical results}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68613}, year = {2010}, abstract = {Background: To introduce a novel method of patient positioning for high precision intracranial radiotherapy. Methods: An infrared(IR)-array, reproducibly attached to the patient via a vacuum-mouthpiece(vMP) and connected to the table via a 6 degree-of-freedom(DoF) mechanical arm serves as positioning and fixation system. After IR-based manual prepositioning to rough treatment position and fixation of the mechanical arm, a cone-beam CT(CBCT) is performed. A robotic 6 DoF treatment couch (HexaPOD™) then automatically corrects all remaining translations and rotations. This absolute position of infrared markers at the first fraction acts as reference for the following fractions where patients are manually prepositioned to within ± 2 mm and ± 2° of this IR reference position prior to final HexaPOD-based correction; consequently CBCT imaging is only required once at the first treatment fraction. The preclinical feasibility and attainable repositioning accuracy of this method was evaluated on a phantom and human volunteers as was the clinical efficacy on 7 pilot study patients. Results: Phantom and volunteer manual IR-based prepositioning to within ± 2 mm and ± 2° in 6DoF was possible within a mean(± SD) of 90 ± 31 and 56 ± 22 seconds respectively. Mean phantom translational and rotational precision after 6 DoF corrections by the HexaPOD was 0.2 ± 0.2 mm and 0.7 ± 0.8° respectively. For the actual patient collective, the mean 3D vector for inter-treatment repositioning accuracy (n = 102) was 1.6 ± 0.8 mm while intra-fraction movement (n = 110) was 0.6 ± 0.4 mm. Conclusions: This novel semi-automatic 6DoF IR-based system has been shown to compare favourably with existing non-invasive intracranial repeat fixation systems with respect to handling, reproducibility and, more importantly, intrafraction rigidity. Some advantages are full cranial positioning flexibility for single and fractionated IGRT treatments and possibly increased patient comfort.}, subject = {Strahlentherapie}, language = {en} } @article{BallesterBolinchesBeidlemanHeinekenetal.2010, author = {Ballester-Bolinches, A. and Beidleman, J. C. and Heineken, H. and Pedraza-Aguilera, M. C.}, title = {Local Classes and Pairwise Mutually Permutable Products of Finite Groups}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68062}, year = {2010}, abstract = {The main aim of the paper is to present some results about products of pairwise mutually permutable subgroups and local classes.}, subject = {Mathematik}, language = {en} } @article{FerranteWimmer2010, author = {Ferrante, Augusto and Wimmer, Harald K.}, title = {Reachability matrices and cyclic matrices}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68074}, year = {2010}, abstract = {We study reachability matrices R(A, b) = [b,Ab, . . . ,An-1b], where A is an n × n matrix over a field K and b is in Kn. We characterize those matrices that are reachability matrices for some pair (A, b). In the case of a cyclic matrix A and an n-vector of indeterminates x, we derive a factorization of the polynomial det(R(A, x)).}, subject = {Mathematik}, language = {en} } @article{EliasSchoulsvandePoletal.2010, author = {Elias, Johannes and Schouls, Leo M. and van de Pol, Ingrid and Keijzers, Wendy C. and Martin, Diana R. and Glennie, Anne and Oster, Philipp and Frosch, Matthias and Vogel, Ulrich and van der Ende, Arie}, title = {Vaccine Preventability of Meningococcal Clone, Greater Aachen Region, Germany}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68083}, year = {2010}, abstract = {No abstract available}, subject = {IMD}, language = {en} } @article{SeefriedMuellerDeubertSchwarzetal.2010, author = {Seefried, Lothar and Mueller-Deubert, Sigrid and Schwarz, Thomas and Lind, Thomas and Mentrup, Birgit and Kober, Melanie and Docheva, Denitsa and Liedert, Astrid and Kassem, Moustapha and Ignatius, Anita and Schieker, Matthias and Claes, Lutz and Wilke, Winfried and Jakob, Franz and Ebert, Regina}, title = {A small scale cell culture system to analyze mechanobiology using reporter gene constructs and polyurethane dishes}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68099}, year = {2010}, abstract = {Mechanical forces are translated into biochemical signals and contribute to cell differentiation and phenotype maintenance. Mesenchymal stem cells and their tissuespecific offspring, as osteoblasts and chondrocytes, cells of cardiovascular tissues and lung cells are sensitive to mechanical loading but molecules and mechanisms involved have to be unraveled. It is well established that cellular mechanotransduction is mediated e.g. by activation of the transcription factor SP1 and by kinase signaling cascades resulting in the activation of the AP1 complex. To investigate cellular mechanisms involved in mechanotransduction and to analyze substances, which modulate cellular mechanosensitivity reporter gene constructs, which can be transfected into cells of interest might be helpful. Suitable small-scale bioreactor systems and mechanosensitive reporter gene constructs are lacking. To analyze the molecular mechanisms of mechanotransduction and its crosstalk with biochemically induced signal transduction, AP1 and SP1 luciferase reporter gene constructs were cloned and transfected into various cell lines and primary cells. A newly developed bioreactor and small-scale 24-well polyurethane dishes were used to apply cyclic stretching to the transfected cells. 1 Hz cyclic stretching for 30 min in this system resulted in a significant stimulation of AP1 and SP1 mediated luciferase activity compared to unstimulated cells. In summary we describe a small-scale cell culture/bioreactor system capable of analyzing subcellular crosstalk mechanisms in mechanotransduction, mechanosensitivity of primary cells and of screening the activity of putative mechanosensitizers as new targets, e.g. for the treatment of bone loss caused by both disuse and signal transduction related alterations of mechanotransduction.}, subject = {Bioreaktor}, language = {en} } @article{GerdesWieserMuehlbergeretal.2010, author = {Gerdes, Antje B. M. and Wieser, Matthias J. and M{\"u}hlberger, Andreas and Weyers, Peter and Alpers, Georg W. and Plichta, Michael M. and Breuer, Felix and Pauli, Paul}, title = {Brain activations to emotional pictures are differentially associated with valence and arousal ratings}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68153}, year = {2010}, abstract = {Several studies have investigated the neural responses triggered by emotional pictures, but the specificity of the involved structures such as the amygdala or the ventral striatum is still under debate. Furthermore, only few studies examined the association of stimuli's valence and arousal and the underlying brain responses. Therefore, we investigated brain responses with functional magnetic resonance imaging of 17 healthy participants to pleasant and unpleasant affective pictures and afterwards assessed ratings of valence and arousal. As expected, unpleasant pictures strongly activated the right and left amygdala, the right hippocampus, and the medial occipital lobe, whereas pleasant pictures elicited significant activations in left occipital regions, and in parts of the medial temporal lobe. The direct comparison of unpleasant and pleasant pictures, which were comparable in arousal clearly indicated stronger amygdala activation in response to the unpleasant pictures. Most important, correlational analyses revealed on the one hand that the arousal of unpleasant pictures was significantly associated with activations in the right amygdala and the left caudate body. On the other hand, valence of pleasant pictures was significantly correlated with activations in the right caudate head, extending to the nucleus accumbens (NAcc) and the left dorsolateral prefrontal cortex. These findings support the notion that the amygdala is primarily involved in processing of unpleasant stimuli, particularly to more arousing unpleasant stimuli. Reward-related structures like the caudate and NAcc primarily respond to pleasant stimuli, the stronger the more positive the valence of these stimuli is.}, subject = {Psychologie}, language = {en} } @article{MuenssingerHalderKleihetal.2010, author = {M{\"u}nßinger, Jana I. and Halder, Sebastian and Kleih, Sonja C. and Furdea, Adrian and Raco, Valerio and H{\"o}sle, Adi and K{\"u}bler, Andrea}, title = {Brain Painting: first evaluation of a new brain-computer interface application with ALS-patients and healthy volunteers}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68168}, year = {2010}, abstract = {Brain-computer interfaces (BCIs) enable paralyzed patients to communicate; however, up to date, no creative expression was possible. The current study investigated the accuracy and user-friendliness of P300-Brain Painting, a new BCI application developed to paint pictures using brain activity only. Two different versions of the P300-Brain Painting application were tested: A colored matrix tested by a group of ALS-patients (n = 3) and healthy participants (n = 10), and a black and white matrix tested by healthy participants (n = 10). The three ALS-patients achieved high accuracies; two of them reaching above 89\% accuracy. In healthy subjects, a comparison between the P300-Brain Painting application (colored matrix) and the P300-Spelling application revealed significantly lower accuracy and P300 amplitudes for the P300-Brain Painting application. This drop in accuracy and P300 amplitudes was not found when comparing the P300-Spelling application to an adapted, black and white matrix of the P300-Brain Painting application. By employing a black and white matrix, the accuracy of the P300-Brain Painting application was significantly enhanced and reached the accuracy of the P300-Spelling application. ALS-patients greatly enjoyed P300-Brain Painting and were able to use the application with the same accuracy as healthy subjects. P300-Brain Painting enables paralyzed patients to express themselves creatively and to participate in the prolific society through exhibitions.}, subject = {Psychologie}, language = {en} } @article{GeissingerSadlerRothetal.2010, author = {Geissinger, Eva and Sadler, Petra and Roth, Sabine and Grieb, Tina and Puppe, Bernhard and Mueller, Nora and Reimer, Peter and Vetter-Kauczok, Claudia S. and Wenzel, Joerg and Bonzheim, Irina and Ruediger, Thomas and Mueller-Hermelink, Hans Konrad and Rosenwald, Andreas}, title = {Disturbed expression of the T-cell receptor/CD3 complex and associated signaling molecules in CD30(+) T-cell lymphoproliferations}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68179}, year = {2010}, abstract = {Background CD30+ T-cell lymphoproliferations comprise a spectrum of clinically heterogeneous entities, including systemic anaplastic large cell lymphomas (ALK- and ALK+) and primary cutaneous CD30+ T-cell lymphoproliferative disorders. While all these entities are characterized by proliferation of highly atypical, anaplastic CD30+ T cells, the expression of T-cell specific antigens in the tumor cells is not consistently detectable. Design and Methods We evaluated biopsies from 19 patients with primary cutaneous CD30+ lymphoproliferative disorders, 38 with ALK- and 33 with ALK+ systemic anaplastic large cell lymphoma. The biopsies were examined for the expression of T-cell receptoraβ/CD3 complex (CD3γ, δ, ε, ζ), transcription factors regulating T-cell receptor expression (ATF1, ATF2, TCF-1, TCF-1a/LEF-1, Ets1), and molecules of T-cell receptor-associated signaling cascades (Lck, ZAP-70, LAT, bcl-10, Carma1, NFATc1, c-Jun, c-Fos, Syk) using immunohistochemistry. Results In comparison to the pattern in 20 peripheral T-cell lymphomas, not otherwise specified, we detected a highly disturbed expression of the T-cell receptor/CD3 complex, TCF-1, TCF- 1a/LEF-1, Lck, ZAP-70, LAT, NFATc1, c-Jun, c-Fos and Syk in most of the systemic anaplastic large cell lymphomas. In addition, primary cutaneous CD30+ lymphoproliferative disorders showed such a similar expression pattern to that of systemic anaplastic large cell lymphomas, that none of the markers we investigated can reliably distinguish between these CD30+ T-cell lymphoproliferations. Conclusions Severely altered expression of the T-cell receptor/CD3 complex, T-cell receptor-associated transcription factors and signal transduction molecules is a common characteristic of systemic and cutaneous CD30+ lymphoproliferations, although the clinical behavior of these entities is very different. Since peripheral T-cell lymphomas, not otherwise specified retain the full expression program required for functioning T-cell receptor signaling, the differential expression of a subset of these markers might be of diagnostic utility in distinguishing peripheral T-cell lymphomas, not otherwise specified from the entire group of CD30+ lymphoproliferations.}, subject = {Medizin}, language = {en} } @techreport{KneitzBroeckerBecker2010, author = {Kneitz, H. and Br{\"o}cker, Eva B. and Becker, JC}, title = {Mycosis fungoides bullosa: a case report and review of the literature}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68233}, year = {2010}, abstract = {Introduction: Mycosis fungoides, the most common type of cutaneous T-cell lymphoma, can manifest in a variety of clinical and histological forms. Bulla formation is an uncommon finding in mycosis fungoides and only approximately 20 cases have been reported in the literature. Case presentation: We present a case of rapidly progressive mycosis fungoides in a 68-year-old Caucasian man who initially presented with erythematous plaques characterised by blister formation. Conclusion: Although mycosis fungoides bullosa is extremely rare, it has to be regarded as an important clinical subtype of cutaneous T-cell lymphoma. Mycosis fungoides bullosa represents a particularly aggressive form of mycosis fungoides and is associated with a poor prognosis. The rapid disease progression in our patient confirms bulla formation as an adverse prognostic sign in cutaneous T-cell lymphoma.}, subject = {Mycosis fungoides bullosa}, language = {en} } @article{GattenloehnerEtschmannKunzmannetal.2010, author = {Gattenl{\"o}hner, S. and Etschmann, B. and Kunzmann, V. and Thalheimer, A. and Hack, M. and Kleber, G. and Einsele, H. and Germer, C. and M{\"u}ller-Hermelink, H.-K.}, title = {Concordance of KRAS/BRAF Mutation Status in Metastatic Colorectal Cancer before and after Anti-EGFR Therapy}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68240}, year = {2010}, abstract = {Anti-EGFR targeted therapy is a potent strategy in the treatment of metastatic colorectal cancer (mCRC) but activating mutations in the KRAS gene are associated with poor response to this treatment. Therefore, KRAS mutation analysis is employed in the selection of patients for EGFR-targeted therapy and various studies have shown a high concordance between the mutation status in primary CRC and corresponding metastases. However, although development of therapy related resistance occurs also in the context of novel drugs such as tyrosine kinase-inhibitors the effect of the anti-EGFR treatment on the KRAS/BRAF mutation status itself in recurrent mCRC has not yet been clarified. Therefore, we analyzed 21mCRCs before/after anti-EGFR therapy and found a pre-/posttherapeutic concordance of the KRAS/BRAF mutation status in 20 of the 21 cases examined. In the one discordant case, further analyses revealed that a tumor mosaicism or multiple primary tumors were present, indicating that anti-EGFR therapy has no influence on KRAS/BRAF mutation status in mCRC. Moreover, as the preselection of patients with a KRASwt genotype for anti-EGFR therapy has become a standard procedure, sample sets such ours might be the basis for future studies addressing the identification of potential anti-EGFR therapy induced genetic alterations apart from KRAS/BRAF mutations.}, subject = {Krebs}, language = {en} } @article{WinterKneitzBroecker2010, author = {Winter, Julia and Kneitz, Hermann and Br{\"o}cker, Eva-B.}, title = {Blood Vessel Density in Basal Cell Carcinomas and Benign Trichogenic Tumors as a Marker for Differential Diagnosis in Dermatopathology}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68275}, year = {2010}, abstract = {In order to get insight into the density of blood vessels in the stroma of benign and malignant trichogenic neoplasms, immunohistological quantification of CD 31 positive vessels was performed in 112 tumors, comprised of 50 BCCs of nodular (35) or morphoeic (15) growth patterns, 17 Pinkus' tumors, as well as 17 trichoepitheliomas of which 6 were desmoplastic, 8 trichofolliculomas, and 20 trichoblastomas. Methods. Vessel density was counted within the tumors, in the tumor-surrounding stroma, and, as a control, in the normal skin of the operation specimen. The results were compared using statistical methods. Results. Whereas, irrespective of the patients' age and location of tumors, the vessel density in normal skin showed no significant differences (8.8 ± 2.7), the counts in the peritumoral stroma revealed significant differences between the different tumors investigated. The highest counts were obtained in BCC (24.7 ± 6.7) and the lowest in benign trichogenic neoplasms (around 14) Pinkus' tumors revealed intermediate counts (19.7 ± 6.6). The vessel densities within the tumors were generally low, and no correlation to the dignity was found. Conclusion. Determination of blood vessel density in the peritumoral stroma may be an additional parameter for differential diagnosis of trichogenic tumors of uncertain dignity.}, subject = {Medizin}, language = {en} } @article{FreyHoubenBroecker2010, author = {Frey, Li­dia M. and Houben, Roland and Br{\"o}cker, Eva-B.}, title = {Pigmentation, Melanocyte Colonization, and p53 Status in Basal Cell Carcinoma}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68283}, year = {2010}, abstract = {Basal cell carcinoma (BCC) is the most common neoplasm in the Caucasian population. Only a fraction of BCC exhibits pigmentation. Lack of melanocyte colonization has been suggested to be due to p53-inactivating mutations in the BCC cells interfering with the p53-proopiomelanocortin pathway and the production of alpha melanocyte-stimulating hormone in the tumor. To evaluate this, we determined tumor pigmentation as well as expression of melan-A and of p53 in 49 BCC tissues bymeans of immunohistochemistry. As expected, we observed a positive relation between tumor pigmentation and melan-A positive intratumoral melanocytes.Melanocyte colonization and, to a lesser extent, p53 overexpression showed intraindividual heterogeneity in larger tumors. p53 overexpression, which is indicative of p53 mutations, was not correlated to melanocyte colonization of BCC. Sequencing of exon 5-8 of the p53 gene in selected BCC cases revealed that colonization by melanocytes and BCC pigmentation is neither ablated by p53 mutations nor generally present in BCCs with wild-type p53.}, subject = {Medizin}, language = {en} } @article{AlbertWeissenbergerSiren2010, author = {Albert-Weissenberger, Christiane and Sir{\´e}n, Anna-Leena}, title = {Experimental traumatic brain injury}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68131}, year = {2010}, abstract = {Traumatic brain injury, a leading cause of death and disability, is a result of an outside force causing mechanical disruption of brain tissue and delayed pathogenic events which collectively exacerbate the injury. These pathogenic injury processes are poorly understood and accordingly no effective neuroprotective treatment is available so far. Experimental models are essential for further clarification of the highly complex pathology of traumatic brain injury towards the development of novel treatments. Among the rodent models of traumatic brain injury the most commonly used are the weight-drop, the fluid percussion, and the cortical contusion injury models. As the entire spectrum of events that might occur in traumatic brain injury cannot be covered by one single rodent model, the design and choice of a specific model represents a major challenge for neuroscientists. This review summarizes and evaluates the strengths and weaknesses of the currently available rodent models for traumatic brain injury.}, subject = {Trauma}, language = {en} } @article{BraeuningerKleinschnitzStoll2010, author = {Braeuninger, Stefan and Kleinschnitz, C. and Stoll, G.}, title = {Interleukin-18 does not influence infarct volume or functional outcome in the early stage after transient focal brain ischemia in mice}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68141}, year = {2010}, abstract = {Interleukin-18 (IL-18) is a proinflammatory cytokine of the interleukin-1 family which is upregulated after cerebral ischemia. The functional role of IL-18 in cerebral ischemia is unknown. In the present study, we compared infarct size in IL-18 knock-out and wild-type mice 24 hours and 48 hours after 1-hour transient middle cerebral artery occlusion (tMCAO). Moreover, the functional outcome was evaluated in a modified Bederson score, foot fault test and grip test. There were no significant differences in infarct size or functional outcome tests between wild-type and IL-18 knock-out mice. These data indicate that the early inflammatory response to cerebral ischemia does not involve IL-18, in contrast to other interleukin-1 family members such as interleukin-1.}, subject = {Interleukin-18}, language = {en} } @phdthesis{Nazeer2010, author = {Nazeer, Ahmed}, title = {Physiological and molecular basis of Azospirillum-Arabidopsis Interaction}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-51673}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2010}, abstract = {The present study was aimed at revealing the early signalling events during the interaction of the diazotrophic soil bacterium Azospirillum brasilense with its host plant Arabidopsis thaliana. Furthermore, taking advantage of the micro array technique, a comprehensive overview of Arabidopsis genes has been undertaken which are affected upon association with A. brasilense The characterization of the early responses of Arabidopsis plants upon inoculation with Azospirillum brasilense strain Sp7 clearly indicated parallels with the initial events in plant pathogen interaction. For instance, not only bacterial preprations (lysates) form Azospirillum elicited an apoplastic alkalinization of the culture medium, but also the live bacteria, which were even more effective. Besides, in a luminol based assay, the bacterial lysates triggered production of the reactive oxygen species (ROS) in the Arabidopsis leaf discs. Interestingly, the elongation factor receptor mutants (efr) were completely insensitive to Azospirillum, suggesting elongation factor Tu (EF-TU) recognition as elicitor by Arabidopsis. This hypothesis was further validated with a bioinformatic approach. The N terminus initial 26 amino acids from Azospirillum EF-TU gene (elf26) showed more similarity to the elf26 sequences of bacteria like Agrobacterium tumefaciens which elicit responses in the plants through EF-TU rather than Pseudomonas syringae where the potent elicitor is flagellin 22. Universal transcriptome profiling of Arabidopsis thaliana seedlings upon inoculation with Azospirillum brasilense over a time course of six, twenty four and ninty six hours revealed very little genetic responses in the early time points. However, a bulk of genes was differentially regulated in 96 hours post inoculation (96hpi). The nature of these genes indicated that the bacterial treatment, among others, greatly affect the processes like cell wall modification, hormone metabolism, stress and secondary metabolism. Additionally expression levels of a numer of transcription factors (TFs) related to basic helix loop helix (BHLH) and MYB domain containing TF families were altered with Azospirillum inoculation. Particularly the BHLH TFs were among the most highly regulated genes. The array results from Azospirillum treated plants were further compared with the already available data emnating from treatment with flagellin 22 (flg22), oligogalacturonides (OGs) and Agrobacterium tumefaciens. Noteworthy, very different set of genes were affected upon inoculation with Azospirillum in relation to other treatments. Secondly a cluster of proteins involved in the biosynthesis of aliphatic glucosinolates (GSL) were uniquely induced upon Sp7 exposure. Genes operating in flavonoid biosynthesis also showed a distinct regulation trend in the comparative analysis. Taken together, the study in question provides insights into the early signalling events in the context of Azospirillum-Arabidopsis association and the bacterial signals recognized by the plants. The array data, at the same time, elucidates the genetic factors of Arabidopsis triggered upon association with Azospirillum brasilense.}, subject = {Azospirillum brasilense}, language = {en} } @article{ConradFritschZeidleretal.2010, author = {Conrad, Christopher and Fritsch, Sebastian and Zeidler, Julian and R{\"u}cker, Gerd and Dech, Stefan}, title = {Per-Field Irrigated Crop Classification in Arid Central Asia Using SPOT and ASTER Data}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68630}, year = {2010}, abstract = {The overarching goal of this research was to explore accurate methods of mapping irrigated crops, where digital cadastre information is unavailable: (a) Boundary separation by object-oriented image segmentation using very high spatial resolution (2.5-5 m) data was followed by (b) identification of crops and crop rotations by means of phenology, tasselled cap, and rule-based classification using high resolution (15-30 m) bi-temporal data. The extensive irrigated cotton production system of the Khorezm province in Uzbekistan, Central Asia, was selected as a study region. Image segmentation was carried out on pan-sharpened SPOT data. Varying combinations of segmentation parameters (shape, compactness, and color) were tested for optimized boundary separation. The resulting geometry was validated against polygons digitized from the data and cadastre maps, analysing similarity (size, shape) and congruence. The parameters shape and compactness were decisive for segmentation accuracy. Differences between crop phenologies were analyzed at field level using bi-temporal ASTER data. A rule set based on the tasselled cap indices greenness and brightness allowed for classifying crop rotations of cotton, winter-wheat and rice, resulting in an overall accuracy of 80 \%. The proposed field-based crop classification method can be an important tool for use in water demand estimations, crop yield simulations, or economic models in agricultural systems similar to Khorezm.}, subject = {Geologie}, language = {en} } @article{SchenkelUhlemann2010, author = {Schenkel, Alexander and Uhlemann, Christoph F.}, title = {Field Theory on Curved Noncommutative Spacetimes}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68648}, year = {2010}, abstract = {We study classical scalar field theories on noncommutative curved spacetimes. Following the approach of Wess et al. [Classical Quantum Gravity 22 (2005), 3511 and Classical Quantum Gravity 23 (2006), 1883], we describe noncommutative spacetimes by using (Abelian) Drinfel'd twists and the associated ?-products and ?-differential geometry. In particular, we allow for position dependent noncommutativity and do not restrict ourselves to the Moyal-Weyl deformation. We construct action functionals for real scalar fields on noncommutative curved spacetimes, and derive the corresponding deformed wave equations. We provide explicit examples of deformed Klein-Gordon operators for noncommutative Minkowski, de Sitter, Schwarzschild and Randall-Sundrum spacetimes, which solve the noncommutative Einstein equations. We study the construction of deformed Green's functions and provide a diagrammatic approach for their perturbative calculation. The leading noncommutative corrections to the Green's functions for our examples are derived.}, subject = {Physik}, language = {en} } @article{SchuppHeidlandStopper2010, author = {Schupp, Nicole and Heidland, August and Stopper, Helga}, title = {Genomic Damage in Endstage Renal Disease - Contribution of Uremic Toxins}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68653}, year = {2010}, abstract = {Patients with end-stage renal disease (ESRD), whether on conservative, peritoneal or hemodialysis therapy, have elevated genomic damage in peripheral blood lymphocytes and an increased cancer incidence, especially of the kidney. The damage is possibly due to accumulation of uremic toxins like advanced glycation endproducts or homocysteine. However, other endogenous substances with genotoxic properties, which are increased in ESRD, could be involved, such as the blood pressure regulating hormones angiotensin II and aldosterone or the inflammatory cytokine TNF-. This review provides an overview of genomic damage observed in ESRD patients, focuses on possible underlying causes and shows modulations of the damage by modern dialysis strategies and vitamin upplementation.}, subject = {Toxin}, language = {en} } @article{GrimmLazariotouKircheretal.2010, author = {Grimm, Martin and Lazariotou, Maria and Kircher, Stefan and Stuermer, Luisa and Reiber, Christoph and Hoefelmayr, Andreas and Gattenloehner, Stefan and Otto, Christoph and Germer, Christoph T. and von Rahden, Burkhard H. A.}, title = {MMP-1 is a (pre-)invasive factor in Barrett-associated esophageal adenocarcinomas and is associated with positive lymph node status}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68293}, year = {2010}, abstract = {Background: Esophageal adenocarcinomas (EACs) arise due to gastroesophageal reflux, with Barrett's esophagus (BE) regarded as precancerous lesion. Matrix metalloproteinases (MMPs) might play a role during the multistep carcinogenetic process. Methods: Expression of MMP-1 and -13 was analyzed in esophageal cancer (n = 41 EAC with BE, n = 19 EAC without BE, and n = 10 esophageal squamous-cell carcinomas, ESCC), furthermore in BE without intraepithelial neoplasia (IN) (n = 18), and the cell line OE-33. MMP-1 was co-labelled with Ki-67 (proliferation), Cdx-2 (marker for intestinal metaplasia, BE) and analyzed on mRNA level. MMP-1 staining results were correlated with clinicopatholocical parameters. Results: On protein level, MMP-1 expression was found in 39 of 41 (95\%) EAC with BE, in 19 of 19 (100\%) EAC without BE, in 6 of 10 (60\%) ESCC, and in 10 of 18 (56\%) BE without IN. No expression of MMP-13 was found in these specimens. Quantification showed 48\% MMP-1 positive cells in EAC with BE, compared to 35\% in adjacent BE (p < 0.05), 44\% in EAC without BE, 32\% in ESCC, and 4\% in BE without IN. Immunofluorescence double staining experiments revealed increased MMP-1 expressing in proliferating cells (MMP-1+/Ki-67+) (r = 0.943 for BE and r = 0.811 for EAC). On mRNA-level, expression of MMP-1 was significantly higher in EAC compared to BE (p = 0.01) and confirmed immunohistochemical staining results. High MMP-1 levels were associated with lymph node metastases but not with poorer survival (p = 0.307). Conclusions: Our findings suggest that MMP-1 plays a role as preinvasive factor in BE-associated EAC. Expression of MMP-1 in proliferating BE and EAC cells suggest malignant proliferation following the clonal expansion model.}, subject = {Medizin}, language = {en} } @article{AbdelmohsenPimentelElardoHanoraetal.2010, author = {Abdelmohsen, Usama Ramadan and Pimentel-Elardo, Sheila M. and Hanora, Amro and Radwan, Mona and Abou-El-Ela, Soad H. and Ahmed, Safwat and Hentschel, Ute}, title = {Isolation, Phylogenetic Analysis and Anti-infective Activity Screening of Marine Sponge-Associated Actinomycetes}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68307}, year = {2010}, abstract = {Terrestrial actinomycetes are noteworthy producers of a multitude of antibiotics, however the marine representatives are much less studied in this regard. In this study, 90 actinomycetes were isolated from 11 different species of marine sponges that had been collected from offshore Ras Mohamed (Egypt) and from Rovinj (Croatia). Phylogenetic characterization of the isolates based on 16S rRNA gene sequencing supported their assignment to 18 different actinomycete genera representing seven different suborders. Fourteen putatively novel species were identified based on sequence similarity values below 98.2\% to other strains in the NCBI database. A putative new genus related to Rubrobacter was isolated on M1 agar that had been amended with sponge extract, thus highlighting the need for innovative cultivation protocols. Testing for anti-infective activities was performed against clinically relevant, Gram-positive (Enterococcus faecalis, Staphylococcus aureus) and Gram-negative (Escherichia coli, Pseudomonas aeruginosa) bacteria, fungi (Candida albicans) and human parasites (Leishmania major, Trypanosoma brucei). Bioactivities against these pathogens were documented for 10 actinomycete isolates. These results show a high diversity of actinomycetes associated with marine sponges as well as highlight their potential to produce anti-infective agents.}, subject = {Biologie}, language = {en} } @article{PimentelElardoKozytskaBugnietal.2010, author = {Pimentel-Elardo, Sheila Marie and Kozytska, Svitlana and Bugni, Tim S. and Ireland, Chris M. and Moll, Heidrun and Hentschel, Ute}, title = {Anti-Parasitic Compounds from Streptomyces sp. Strains Isolated from Mediterranean Sponges}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68312}, year = {2010}, abstract = {Actinomycetes are prolific producers of pharmacologically important compounds accounting for about 70\% of the naturally derived antibiotics that are currently in clinical use. In this study, we report on the isolation of Streptomyces sp. strains from Mediterranean sponges, on their secondary metabolite production and on their screening for anti-infective activities. Bioassay-guided isolation and purification yielded three previously known compounds namely, cyclic depsipeptide valinomycin, indolocarbazole alkaloid staurosporine and butenolide. This is the first report of the isolation of valinomycin from a marine source. These compounds exhibited novel anti-parasitic activities specifically against Leishmania major (valinomycin IC50 < 0.11 μM; staurosporine IC50 5.30 μM) and Trypanosoma brucei brucei (valinomycin IC50 0.0032 μM; staurosporine IC50 0.022 μM; butenolide IC50 31.77 μM). These results underscore the potential of marine actinomycetes to produce bioactive compounds as well as the re-evaluation of previously known compounds for novel anti-infective activities.}, subject = {Biologie}, language = {en} } @article{PuetzVogiatziStieweetal.2010, author = {Puetz, Stephanie M. and Vogiatzi, Fotini and Stiewe, Thorsten and Sickmann, Albert}, title = {Malignant transformation in a defined genetic background: proteome changes displayed by 2D-PAGE}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68321}, year = {2010}, abstract = {Background: Cancer arises from normal cells through the stepwise accumulation of genetic alterations. Cancer development can be studied by direct genetic manipulation within experimental models of tumorigenesis. Thereby, confusion by the genetic heterogeneity of patients can be circumvented. Moreover, identification of the critical changes that convert a pre-malignant cell into a metastatic, therapy resistant tumor cell, however, is one necessary step to develop effective and selective anti-cancer drugs. Thus, for the current study a cell culture model for malignant transformation was used: Primary human fibroblasts of the BJ strain were sequentially transduced with retroviral vectors encoding the genes for hTERT (cell line BJ-T), simian virus 40 early region (SV40 ER, cell line BJ-TE) and H-Ras V12 (cell line BJ-TER). Results: The stepwise malignant transformation of human fibroblasts was analyzed on the protein level by differential proteome analysis. We observed 39 regulated protein spots and therein identified 67 different proteins. The strongest change of spot patterns was detected due to integration of SV40 ER. Among the proteins being significantly regulated during the malignant transformation process well known proliferating cell nuclear antigen (PCNA) as well as the chaperones mitochondrial heat shock protein 75 kDa (TRAP-1) and heat shock protein HSP90 were identified. Moreover, we find out, that TRAP-1 is already up-regulated by means of SV40 ER expression instead of H-Ras V12. Furthermore Peroxiredoxin-6 (PRDX6), Annexin A2 (p36), Plasminogen activator inhibitor 2 (PAI-2) and Keratin type II cytoskeletal 7 (CK-7) were identified to be regulated. For some protein candidates we confirmed our 2D-PAGE results by Western Blot. Conclusion: These findings give further hints for intriguing interactions between the p16-RB pathway, the mitochondrial chaperone network and the cytoskeleton. In summary, using a cell culture model for malignant transformation analyzed with 2D-PAGE, proteome and cellular changes can be related to defined steps of tumorigenesis.}, subject = {Medizin}, language = {en} } @article{MeierjohannHufnagelWendeetal.2010, author = {Meierjohann, Svenja and Hufnagel, Anita and Wende, Elisabeth and Kleinschmidt, Markus A. and Wolf, Katarina and Friedl, Peter and Gaubatz, Stefan and Schartl, Manfred}, title = {MMP13 mediates cell cycle progression in melanocytes and melanoma cells: in vitro studies of migration and proliferation}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68335}, year = {2010}, abstract = {Background: Melanoma cells are usually characterized by a strong proliferative potential and efficient invasive migration. Among the multiple molecular changes that are recorded during progression of this disease, aberrant activation of receptor tyrosine kinases (RTK) is often observed. Activation of matrix metalloproteases goes along with RTK activation and usually enhances RTK-driven migration. The purpose of this study was to examine RTKdriven three-dimensional migration of melanocytes and the pro-tumorigenic role of matrix metalloproteases for melanocytes and melanoma cells. Results: Using experimental melanocyte dedifferentiation as a model for early melanomagenesis we show that an activated EGF receptor variant potentiates migration through three-dimensional fibrillar collagen. EGFR stimulation also resulted in a strong induction of matrix metalloproteases in a MAPK-dependent manner. However, neither MAPK nor MMP activity were required for migration, as the cells migrated in an entirely amoeboid mode. Instead, MMPs fulfilled a function in cell cycle regulation, as their inhibition resulted in strong growth inhibition of melanocytes. The same effect was observed in the human melanoma cell line A375 after stimulation with FCS. Using sh- and siRNA techniques, we could show that MMP13 is the protease responsible for this effect. Along with decreased proliferation, knockdown of MMP13 strongly enhanced pigmentation of melanocytes. Conclusions: Our data show for the first time that growth stimuli are mediated via MMP13 in melanocytes and melanoma, suggesting an autocrine MMP13-driven loop. Given that MMP13-specific inhibitors are already developed, these results support the evaluation of these inhibitors in the treatment of melanoma.}, subject = {Medizin}, language = {en} } @article{ChenBoettgerReifetal.2010, author = {Chen, Yong and Boettger, Michael K. and Reif, Andreas and Schmitt, Angelika and Ueceyler, Nurcan and Sommer, Claudia}, title = {Nitric oxide synthase modulates CFA-induced thermal hyperalgesia through cytokine regulation in mice}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68349}, year = {2010}, abstract = {Background: Although it has been largely demonstrated that nitric oxide synthase (NOS), a key enzyme for nitric oxide (NO) production, modulates inflammatory pain, the molecular mechanisms underlying these effects remain to be clarified. Here we asked whether cytokines, which have well-described roles in inflammatory pain, are downstream targets of NO in inflammatory pain and which of the isoforms of NOS are involved in this process. Results: Intraperitoneal (i.p.) pretreatment with 7-nitroindazole sodium salt (7-NINA, a selective neuronal NOS inhibitor), aminoguanidine hydrochloride (AG, a selective inducible NOS inhibitor), L-N(G)-nitroarginine methyl ester (L-NAME, a non-selective NOS inhibitor), but not L-N(5)-(1-iminoethyl)-ornithine (L-NIO, a selective endothelial NOS inhibitor), significantly attenuated thermal hyperalgesia induced by intraplantar (i.pl.) injection of complete Freund's adjuvant (CFA). Real-time reverse transcription-polymerase chain reaction (RT-PCR) revealed a significant increase of nNOS, iNOS, and eNOS gene expression, as well as tumor necrosis factor-alpha (TNF), interleukin-1 beta (IL-1b), and interleukin-10 (IL-10) gene expression in plantar skin, following CFA. Pretreatment with the NOS inhibitors prevented the CFA-induced increase of the pro-inflammatory cytokines TNF and IL-1b. The increase of the antiinflammatory cytokine IL-10 was augmented in mice pretreated with 7-NINA or L-NAME, but reduced in mice receiving AG or L-NIO. NNOS-, iNOS- or eNOS-knockout (KO) mice had lower gene expression of TNF, IL-1b, and IL-10 following CFA, overall corroborating the inhibitor data. Conclusion: These findings lead us to propose that inhibition of NOS modulates inflammatory thermal hyperalgesia by regulating cytokine expression.}, subject = {Medizin}, language = {en} } @article{Zeeshan2010, author = {Zeeshan, Ahmed}, title = {Towards Performance Measurement and Metrics Based Analysis of PLA Applications}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68188}, year = {2010}, abstract = {This article is about a measurement analysis based approach to help software practitioners in managing the additional level complexities and variabilities in software product line applications. The architecture of the proposed approach i.e. ZAC is designed and implemented to perform preprocessesed source code analysis, calculate traditional and product line metrics and visualize results in two and three dimensional diagrams. Experiments using real time data sets are performed which concluded with the results that the ZAC can be very helpful for the software practitioners in understanding the overall structure and complexity of product line applications. Moreover the obtained results prove strong positive correlation between calculated traditional and product line measures.}, subject = {Programmierbare logische Anordnung}, language = {en} } @article{KuehnPradel2010, author = {Kuehn, Andrea and Pradel, Gabriele}, title = {The Coming-Out of Malaria Gametocytes [Review Article]}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68196}, year = {2010}, abstract = {The tropical disease malaria, which results in more than one million deaths annually, is caused by protozoan parasites of the genus Plasmodium and transmitted by blood-feeding Anopheline mosquitoes. Parasite transition from the human host to the mosquito vector is mediated by gametocytes, sexual stages that are formed in human erythrocytes, which therefore play a crucial part in the spread of the tropical disease. The uptake by the blood-feeding mosquito triggers important molecular and cellular changes in the gametocytes, thus mediating the rapid adjustment of the parasite from the warm-blooded host to the insect host and subsequently initiating reproduction. The contact with midgut factors triggers gametocyte activation and results in their egress from the enveloping erythrocyte, which then leads to gamete formation and fertilization. This review summarizes recent findings on the role of gametocytes during transmission to themosquito and particularly focuses on the molecular mechanisms underlying gametocyte activation and emergence from the host erythrocyte during gametogenesis.}, subject = {Malaria}, language = {en} } @article{GattenloehnerJoerissenHuhnetal.2010, author = {Gattenloehner, Stefan and Joerissen, H. and Huhn, M. and Vincent, A. and Beeson, D. and Tzartos, S. and Mamalaki, A. and Etschmann, B. and Muller-Hermelink, H. K. and Koscielniak, E. and Barth, S. and Marx, A.}, title = {A Human Recombinant Autoantibody-Based Immunotoxin Specific for the Fetal Acetylcholine Receptor Inhibits Rhabdomyosarcoma Growth In Vitro and in a Murine Transplantation Model [Research Article]}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68200}, year = {2010}, abstract = {Rhabdomyosarcoma (RMS) is the most common malignant soft tissue tumor in children and is highly resistant to all forms of treatment currently available once metastasis or relapse has commenced. As it has recently been determined that the acetylcholine receptor (AChR) γ-subunit, which defines the fetal AChR (fAChR) isoform, is almost exclusively expressed in RMS post partum, we recombinantly fused a single chain variable fragment (scFv) derived from a fully human anti-fAChR Fab-fragment to Pseudomonas exotoxin A to generate an anti-fAChR immunotoxin (scFv35-ETA).While scFv35-ETA had no damaging effect on fAChR-negative control cell lines, it killed human embryonic and alveolar RMS cell lines in vitro and delayed RMS development in a murine transplantation model. These results indicate that scFv35-ETA may be a valuable new therapeutic tool as well as a relevant step towards the development of a fully human immunotoxin directed against RMS. Moreover, as approximately 20\% of metastatic malignant melanomas (MMs) display rhabdoid features including the expression of fAChR, the immunotoxin we developed may also prove to be of significant use in the treatment of these more common and most often fatal neoplasms.}, subject = {Medizin}, language = {en} } @article{ParczykHeroldKlugetal.2010, author = {Parczyk, Marco and Herold, Volker and Klug, Gert and Bauer, Wolfgang R. and Rommel, Eberhard and Jakob, Peter M.}, title = {Regional in vivo transit time measurements of aortic pulse wave velocity in mice with high-field CMR at 17.6 Tesla}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68219}, year = {2010}, abstract = {Background: Transgenic mouse models are increasingly used to study the pathophysiology of human cardiovascular diseases. The aortic pulse wave velocity (PWV) is an indirect measure for vascular stiffness and a marker for cardiovascular risk. Results: This study presents a cardiovascular magnetic resonance (CMR) transit time (TT) method that allows the determination of the PWV in the descending murine aorta by analyzing blood flow waveforms. Systolic flow pulses were recorded with a temporal resolution of 1 ms applying phase velocity encoding. In a first step, the CMR method was validated by pressure waveform measurements on a pulsatile elastic vessel phantom. In a second step, the CMR method was applied to measure PWVs in a group of five eight-month-old apolipoprotein E deficient (ApoE(-/-)) mice and an age matched group of four C57Bl/6J mice. The ApoE(-/-) group had a higher mean PWV (PWV = 3.0 ± 0.6 m/s) than the C57Bl/6J group (PWV = 2.4 ± 0.4 m/s). The difference was statistically significant (p = 0.014). Conclusions: The findings of this study demonstrate that high field CMR is applicable to non-invasively determine and distinguish PWVs in the arterial system of healthy and diseased groups of mice.}, subject = {Medizin}, language = {en} } @article{BollazziRoces2010, author = {Bollazzi, Martin and Roces, Flavio}, title = {The thermoregulatory function of thatched nests in the South American grass-cutting ant, Acromyrmex heyeri}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68225}, year = {2010}, abstract = {The construction of mound-shaped nests by ants is considered as a behavioral adaptation to low environmental temperatures, i.e., colonies achieve higher and more stables temperatures than those of the environment. Besides the well-known nests of boreal Formica wood-ants, several species of South American leaf-cutting ants of the genus Acromyrmex construct thatched nests. Acromyrmex workers import plant fragments as building material, and arrange them so as to form a thatch covering a central chamber, where the fungus garden is located. Thus, the degree of thermoregulation attained by the fungus garden inside the thatched nest largely depends on how the thatch affects the thermal relations between the fungus and the environment. This work was aimed at studying the thermoregulatory function of the thatched nests built by the grass-cutting ant Acromyrmex heyeri Forel (Hymenoptera: Formicidae: Myrmicinae). Nest and environmental temperatures were measured as a function of solar radiation on the long-term. The thermal diffusivity of the nest thatch was measured and compared to that of the surrounding soil, in order to assess the influence of the building material on the nest's thermoregulatory ability. The results showed that the average core temperature of thatched nests was higher than that of the environment, but remained below values harmful for the fungus. This thermoregulation was brought about by the low thermal diffusivity of the nest thatch built by workers with plant fragments, instead of the readily-available soil particles that have a higher thermal diffusivity. The thatch prevented diurnal nest overheating by the incoming solar radiation, and avoided losses of the accumulated daily heat into the cold air during the night. The adaptive value of thatching behavior in Acromyrmex leaf-cutting ants occurring in the southernmost distribution range is discussed.}, subject = {Acromyrmex heyeri}, language = {en} } @article{KraftSchwarzPochetetal.2010, author = {Kraft, P. and Schwarz, T. and Pochet, L. and Stoll, G. and Kleinschnitz, Christoph}, title = {COU254, a specific 3-carboxamide-coumarin inhibitor of coagulation factor XII, does not protect mice from acute ischemic stroke}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68103}, year = {2010}, abstract = {Background: Anticoagulation is an important means to prevent from acute ischemic stroke but is associated with a significant risk of severe hemorrhages. Previous studies have shown that blood coagulation factor XII (FXII)- deficient mice are protected from pathological thrombus formation during cerebral ischemia without bearing an increased bleeding tendency. Hence, pharmacological blockade of FXII might be a promising and safe approach to prevent acute ischemic stroke and possibly other thromboembolic disorders but pharmacological inhibitors selective over FXII are still lacking. In the present study we investigated the efficacy of COU254, a novel nonpeptidic 3-carboxamide-coumarin that selectively blocks FXII activity, on stroke development and post stroke functional outcome in mice. Methods: C57Bl/6 mice were treated with COU254 (40 mg/kg i.p.) or vehicle and subjected to 60 min transient middle cerebral artery occlusion (tMCAO) using the intraluminal filament method. After 24 h infarct volumes were determined from 2,3,5-Triphenyltetrazoliumchloride(TTC)-stained brain sections and functional scores were assessed. Hematoxylin and eosin (H\&E) staining was used to estimate the extent of neuronal cell damage. Thrombus formation within the infarcted brain areas was analyzed by immunoblot. Results: Infarct volumes and functional outcomes on day 1 after tMCAO did not significantly differ between COU254 pre-treated mice or untreated controls (p > 0.05). Histology revealed extensive ischemic neuronal damage regularly including the cortex and the basal ganglia in both groups. COU254 treatment did not prevent intracerebral fibrin(ogen) formation. Conclusions: COU254 at the given concentration of 40 mg/kg failed to demonstrate efficacy in acute ischemic stroke in this preliminary study. Further preclinical evaluation of 3-carboxamide-coumarins is needed before the antithrombotic potential of this novel class of FXII inhibitors can be finally judged.}, subject = {Schlaganfall}, language = {en} } @article{PhamHelluyBraeuningeretal.2010, author = {Pham, Mirko and Helluy, X. and Braeuninger, S. and Jakob, P. and Stoll, G. and Kleinschnitz, Christoph and Bendszus, M.}, title = {Outcome of experimental stroke in C57Bl/6 and Sv/129 mice assessed by multimodal ultra-high field MRI}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68115}, year = {2010}, abstract = {Transgenic mice bred on C57Bl/6 or Sv/129 genetic background are frequently used in stroke research. It is well established that variations in cerebrovascular anatomy and hemodynamics can influence stroke outcome in different inbred mouse lines. We compared stroke development in C57Bl/6 and Sv/129 mice in the widely used model of transient middle cerebral artery occlusion (tMCAO) by multimodal ultra-high field magnetic resonance imaging (MRI). C57Bl/6 and Sv/129 mice underwent 60 min of tMCAO and were analyzed by MRI 2 h and 24 h afterwards. Structural and functional images were registered to a standard anatomical template. Probability maps of infarction were rendered by automated segmentation from quantitative T2-relaxometric images. Whole-brain segmentation of infarction was accomplished manually on high-resolution T2-weighted (T2-w) RARE images. Cerebral perfusion (cerebral blood flow, CBF) was measured quantitatively by modified continuous arterial-spin-labeling (CASL) and apparent diffusion coefficients (ADC) by spin-echo diffusion-weighted imaging (DWI). Probabilities of cortical (95.1\% ± 3.1 vs. 92.1\% ± 2.5; p > 0.05) and subcortical (100\% vs. 100\%; p > 0.05) infarctions at 24 h were similar in both groups as was the whole-brain volumetric extent of cerebral infarction. In addition, CBF and ADC values did not differ between C57Bl/6 and Sv/129 mice at any time point or region of interest. The C57Bl/6 and Sv/129 genetic background is no major confounding factor of infarct size and cerebral perfusion in the tMCAO model.}, subject = {NMR-Tomographie}, language = {en} } @article{EhlingBittnerBobaketal.2010, author = {Ehling, P. and Bittner, S. and Bobak, N. and Schwarz, T. and Wiendl, H. and Budde, T. and Kleinschnitz, Christoph and Meuth, S. G.}, title = {Two pore domain potassium channels in cerebral ischemia: a focus on K2p9.1 (TASK3, KCNK9)}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68129}, year = {2010}, abstract = {BACKGROUND: Recently, members of the two-pore domain potassium channel family (K2P channels) could be shown to be involved in mechanisms contributing to neuronal damage after cerebral ischemia. K2P3.1-/- animals showed larger infarct volumes and a worse functional outcome following experimentally induced ischemic stroke. Here, we question the role of the closely related K2P channel K2P9.1. METHODS: We combine electrophysiological recordings in brain-slice preparations of wildtype and K2P9.1-/- mice with an in vivo model of cerebral ischemia (transient middle cerebral artery occlusion (tMCAO)) to depict a functional impact of K2P9.1 in stroke formation. RESULTS: Patch-clamp recordings reveal that currents mediated through K2P9.1 can be obtained in slice preparations of the dorsal lateral geniculate nucleus (dLGN) as a model of central nervous relay neurons. Current characteristics are indicative of K2P9.1 as they display an increase upon removal of extracellular divalent cations, an outward rectification and a reversal potential close to the potassium equilibrium potential. Lowering extracellular pH values from 7.35 to 6.0 showed comparable current reductions in neurons from wildtype and K2P9.1-/- mice (68.31 +/- 9.80\% and 69.92 +/- 11.65\%, respectively). These results could be translated in an in vivo model of cerebral ischemia where infarct volumes and functional outcomes showed a none significant tendency towards smaller infarct volumes in K2P9.1-/- animals compared to wildtype mice 24 hours after 60 min of tMCAO induction (60.50 +/- 17.31 mm3 and 47.10 +/- 19.26 mm3, respectively). CONCLUSIONS: Together with findings from earlier studies on K2P2.1-/- and K2P3.1-/- mice, the results of the present study on K2P9.1-/- mice indicate a differential contribution of K2P channel subtypes to the diverse and complex in vivo effects in rodent models of cerebral ischemia.}, subject = {Kaliumkanal}, language = {en} } @phdthesis{Foerster2010, author = {F{\"o}rster, Frank}, title = {Making the most of phylogeny: Unique adaptations in tardigrades and 216374 internal transcribed spacer 2 structures}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-51466}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2010}, abstract = {The phylum Tardigrada consists of about 1000 described species to date. The animals live in habitats within marine, freshwater and terrestrial ecosystems allover the world. Tardigrades are polyextremophiles. They are capable to resist extreme temperature, pressure or radiation. In the event of desiccation, tardigrades enter a so-called tun stage. The reason for their great tolerance capabilities against extreme environmental conditions is not discovered yet. Our Funcrypta project aims at finding answers to the question what mechanisms underlie these adaption capabilities particularly with regard to the species Milnesium tardigradum. The first part of this thesis describes the establishment of expressed sequence tags (ESTs) libraries for different stages of M. tardigradum. From proteomics data we bioinformatically identified 144 proteins with a known function and additionally 36 proteins which seemed to be specific for M. tardigradum. The generation of a comprehensive web-based database allows us to merge the proteome and transcriptome data. Therefore we created an annotation pipeline for the functional annotation of the protein and nucleotide sequences. Additionally, we clustered the obtained proteome dataset and identified some tardigrade-specific proteins (TSPs) which did not show homology to known proteins. Moreover, we examined the heat shock proteins of M. tardigradum and their different expression levels depending on the actual state of the animals. In further bioinformatical analyses of the whole data set, we discovered promising proteins and pathways which are described to be correlated with the stress tolerance, e.g. late embryogenesis abundant (LEA) proteins. Besides, we compared the tardigrades with nematodes, rotifers, yeast and man to identify shared and tardigrade specific stress pathways. An analysis of the 50 and 30 untranslated regions (UTRs) demonstrates a strong usage of stabilising motifs like the 15-lipoxygenase differentiation control element (15-LOX-DICE) but also reveals a lack of other common UTR motifs normally used, e.g. AU rich elements. The second part of this thesis focuses on the relatedness between several cryptic species within the tardigrade genus Paramacrobiotus. Therefore for the first time, we used the sequence-structure information of the internal transcribed spacer 2 (ITS2) as a phylogenetic marker in tardigrades. This allowed the description of three new species which were indistinguishable using morphological characters or common molecular markers like the 18S ribosomal ribonucleic acid (rRNA) or the Cytochrome c oxidase subunit I (COI). In a large in silico simulation study we also succeeded to show the benefit for the phylogenetic tree reconstruction by adding structure information to the ITS2 sequence. Next to the genus Paramacrobiotus we used the ITS2 to corroborate a monophyletic DO-group (Sphaeropleales) within the Chlorophyceae. Additionally we redesigned another comprehensive database—the ITS2 database resulting in a doubled number of sequence-structure pairs of the ITS2. In conclusion, this thesis shows the first insights (6 first author publications and 4 coauthor publications) into the reasons for the enormous adaption capabilities of tardigrades and offers a solution to the debate on the phylogenetic relatedness within the tardigrade genus Paramacrobiotus.}, subject = {Phylogenie}, language = {en} } @article{BraunschweigDewhurstSchwabetal.2010, author = {Braunschweig, Holger and Dewhurst, Rian D. and Schwab, Katrin and Wagner, Katharina}, title = {{N ',N ''-Bis[2,6-bis(1-methylethyl)phenyl]-N,N-dimethylguanidinato-kappa N-2 ',N ''}dibromidoborane}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-67622}, year = {2010}, abstract = {In the molecular structure of the title compound, C27H40N3BBr2, the B atom is connected to two bromide substituents and a guanidinate scaffold, forming a four- membered ring. An aryl group is connected to each N atom in the ring that contains two isopropyl groups in positions 2 and 6.}, subject = {Anorganische Chemie}, language = {en} } @article{BraunschweigDamme2010, author = {Braunschweig, Holger and Damme, Alexander}, title = {1,2-Bis(dimethylamino)-1,2-bis(2,4,6-triisopropylphenyl)diborane(4)}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-67639}, year = {2010}, abstract = {In the molecular structure of the title compound, C34H58B2N2, each B atom of the diborane(4) is connected to one dimethylamino group and one Tip ligand (Tip = 2,4,6-triisopropylphenyl). These findings indicate that the increased steric demand of the Tip groups exerts influence solely on the B—B separation but not on the overall geometry of the title compound.}, subject = {Anorganische Chemie}, language = {en} } @article{BeckMorbachBeeretal.2010, author = {Beck, Christine and Morbach, Henner and Beer, Meinrad and Stenzel, Martin and Tappe, Dennis and Gattenl{\"o}hner, Stefan and Hofmann, Ulrich and Raab, Peter and Girschick, Hermann J.}, title = {Chronic nonbacterial osteomyelitis in childhood: prospective follow-up during the first year of anti-inflammatory treatment}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-67792}, year = {2010}, abstract = {Introduction: Chronic nonbacterial osteomyelitis (CNO) is an inflammatory disorder of unknown etiology. In children and adolescents CNO predominantly affects the metaphyses of the long bones, but lesions can occur at any site of the skeleton. Prospectively followed cohorts using a standardized protocol in diagnosis and treatment have rarely been reported. Methods: Thirty-seven children diagnosed with CNO were treated with naproxen continuously for the first 6 months. If assessment at that time revealed progressive disease or no further improvement, sulfasalazine and short-term corticosteroids were added. The aims of our short-term follow-up study were to describe treatment response in detail and to identify potential risk factors for an unfavorable outcome. Results: Naproxen treatment was highly effective in general, inducing a symptom-free status in 43\% of our patients after 6 months. However, four nonsteroidal anti-inflammatory drug (NSAID) partial-responders were additionally treated with sulfasalazine and short-term corticosteroids. The total number of clinical detectable lesions was significantly reduced. Mean disease activity estimated by the patient/physician and the physical aspect of health-related quality of life including functional ability (global assessment/childhood health assessment questionnaire and childhood health assessment questionnaire) and pain improved significantly. Forty-one percent of our patients showed radiological relapses, but 67\% of them were clinically silent. Conclusions: Most children show a favorable clinical course in the first year of anti-inflammatory treatment with NSAIDs. Relapses and new radiological lesions can occur at any time and at any site in the skeleton but may not be clinically symptomatic. Whole-body magnetic resonance imaging proved to be very sensitive for initial and follow-up diagnostics.}, subject = {Mikrobiologie}, language = {en} } @article{HomannQamarSerimetal.2010, author = {Homann, Arne and Qamar, Riaz-ul and Serim, Sevnur and Dersch, Petra and Seibel, Juergen}, title = {Bioorthogonal metabolic glycoengineering of human larynx carcinoma (HEp-2) cells targeting sialic acid}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-67806}, year = {2010}, abstract = {Sialic acids are located at the termini of mammalian cell-surface glycostructures, which participate in essential interaction processes including adhesion of pathogens prior to infection and immunogenicity. Here we present the synthesis and bioorthogonal metabolic incorporation of the sialic acid analogue N-(1-oxohex-5-ynyl)neuraminic acid (Neu5Hex) into the cell-surface glycocalyx of a human larynx carcinoma cell line (HEp-2) and its fluorescence labelling by click chemistry.}, subject = {Organische Chemie}, language = {en} } @article{PratiharGhoshStepanenkoetal.2010, author = {Pratihar, Pampa and Ghosh, Suhrit and Stepanenko, Vladimir and Patwardhan, Sameer and Grozema, Ferdinand C. and Siebbeles, Laurens D. A. and W{\"u}rthner, Frank}, title = {Self-assembly and semiconductivity of an oligothiophene supergelator}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-67817}, year = {2010}, abstract = {A bis(trialkoxybenzamide)-functionalized quaterthiophene derivative was synthesized and its self-assembly properties in solution were studied. In non-polar solvents such as cyclohexane, this quaterthiophene π-system formed fibril aggregates with an H-type molecular arrangement due to synergistic effect of hydrogen bonding and π-stacking. The self-assembled fibres were found to gelate numerous organic solvents of diverse polarity. The charge transport ability of such elongated fibres of quaterthiophene π-system was explored by the pulse radiolysis time resolved microwave conductivity (PR-TRMC) technique and moderate mobility values were obtained. Furthermore, initial AFM and UV-vis spectroscopic studies of a mixture of our electron-rich quaterthiophene derivative with the electron acceptor [6,6]-phenyl-C61-butyric acid methyl ester (PCBM) revealed a nanoscale segregated assembly of the individual building blocks in the blend.}, subject = {Organische Chemie}, language = {en} } @article{ShityakovDandekar2010, author = {Shityakov, Sergey and Dandekar, Thomas}, title = {Lead expansion and virtual screening of Indinavir derivate HIV-1 protease inhibitors using pharmacophoric - shape similarity scoring function}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-67824}, year = {2010}, abstract = {Indinavir (Crivaxan®) is a potent inhibitor of the HIV (human immunodeficiency virus) protease. This enzyme has an important role in viral replication and is considered to be very attractive target for new antiretroviral drugs. However, it becomes less effective due to highly resistant new viral strains of HIV, which have multiple mutations in their proteases. For this reason, we used a lead expansion method to create a new set of compounds with a new mode of action to protease binding site. 1300 compounds chemically diverse from the initial hit were generated and screened to determine their ability to interact with protease and establish their QSAR properties. Further computational analyses revealed one unique compound with different protease binding ability from the initial hit and its role for possible new class of protease inhibitors is discussed in this report.}, subject = {Proteasen}, language = {en} } @article{KellerFoersterMuelleretal.2010, author = {Keller, Alexander and Foerster, Frank and Mueller, Tobias and Dandekar, Thomas and Schultz, Joerg and Wolf, Matthias}, title = {Including RNA secondary structures improves accuracy and robustness in reconstruction of phylogenetic trees}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-67832}, year = {2010}, abstract = {Background: In several studies, secondary structures of ribosomal genes have been used to improve the quality of phylogenetic reconstructions. An extensive evaluation of the benefits of secondary structure, however, is lacking. Results: This is the first study to counter this deficiency. We inspected the accuracy and robustness of phylogenetics with individual secondary structures by simulation experiments for artificial tree topologies with up to 18 taxa and for divergency levels in the range of typical phylogenetic studies. We chose the internal transcribed spacer 2 of the ribosomal cistron as an exemplary marker region. Simulation integrated the coevolution process of sequences with secondary structures. Additionally, the phylogenetic power of marker size duplication was investigated and compared with sequence and sequence-structure reconstruction methods. The results clearly show that accuracy and robustness of Neighbor Joining trees are largely improved by structural information in contrast to sequence only data, whereas a doubled marker size only accounts for robustness. Conclusions: Individual secondary structures of ribosomal RNA sequences provide a valuable gain of information content that is useful for phylogenetics. Thus, the usage of ITS2 sequence together with secondary structure for taxonomic inferences is recommended. Other reconstruction methods as maximum likelihood, bayesian inference or maximum parsimony may equally profit from secondary structure inclusion. Reviewers: This article was reviewed by Shamil Sunyaev, Andrea Tanzer (nominated by Frank Eisenhaber) and Eugene V. Koonin. Open peer review: Reviewed by Shamil Sunyaev, Andrea Tanzer (nominated by Frank Eisenhaber) and Eugene V. Koonin. For the full reviews, please go to the Reviewers' comments section.}, subject = {Phylogenie}, language = {en} }