@article{SchneiderTautzGruenewaldetal.2012, author = {Schneider, Christof W. and Tautz, J{\"u}rgen and Gr{\"u}newald, Bernd and Fuchs, Stefan}, title = {RFID Tracking of Sublethal Effects of Two Neonicotinoid Insecticides on the Foraging Behavior of Apis mellifera}, series = {PLoS One}, volume = {7}, journal = {PLoS One}, number = {1}, doi = {10.1371/journal.pone.0030023}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-131753}, pages = {e30023}, year = {2012}, abstract = {The development of insecticides requires valid risk assessment procedures to avoid causing harm to beneficial insects and especially to pollinators such as the honeybee Apis mellifera. In addition to testing according to current guidelines designed to detect bee mortality, tests are needed to determine possible sublethal effects interfering with the animal's vitality and behavioral performance. Several methods have been used to detect sublethal effects of different insecticides under laboratory conditions using olfactory conditioning. Furthermore, studies have been conducted on the influence insecticides have on foraging activity and homing ability which require time-consuming visual observation. We tested an experimental design using the radiofrequency identification (RFID) method to monitor the influence of sublethal doses of insecticides on individual honeybee foragers on an automated basis. With electronic readers positioned at the hive entrance and at an artificial food source, we obtained quantifiable data on honeybee foraging behavior. This enabled us to efficiently retrieve detailed information on flight parameters. We compared several groups of bees, fed simultaneously with different dosages of a tested substance. With this experimental approach we monitored the acute effects of sublethal doses of the neonicotinoids imidacloprid (0.15-6 ng/bee) and clothianidin (0.05-2 ng/bee) under field-like circumstances. At field-relevant doses for nectar and pollen no adverse effects were observed for either substance. Both substances led to a significant reduction of foraging activity and to longer foraging flights at doses of >= 0.5 ng/bee (clothianidin) and >= 1.5 ng/bee (imidacloprid) during the first three hours after treatment. This study demonstrates that the RFID-method is an effective way to record short-term alterations in foraging activity after insecticides have been administered once, orally, to individual bees. We contribute further information on the understanding of how honeybees are affected by sublethal doses of insecticides.}, language = {en} } @article{PilsKoppPetersonetal.2012, author = {Pils, Stefan and Kopp, Kathrin and Peterson, Lisa and Tascon, Julia Delgado and Nyffenegger-Jann, Naja J. and Hauck, Christof R.}, title = {The Adaptor Molecule Nck Localizes the WAVE Complex to Promote Actin Polymerization during CEACAM3-Mediated Phagocytosis of Bacteria}, series = {PLoS One}, volume = {7}, journal = {PLoS One}, number = {3}, doi = {10.1371/journal.pone.0032808}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-131747}, pages = {e32808}, year = {2012}, abstract = {Background: CEACAM3 is a granulocyte receptor mediating the opsonin-independent recognition and phagocytosis of human-restricted CEACAM-binding bacteria. CEACAM3 function depends on an intracellular immunoreceptor tyrosine-based activation motif (ITAM)-like sequence that is tyrosine phosphorylated by Src family kinases upon receptor engagement. The phosphorylated ITAM-like sequence triggers GTP-loading of Rac by directly associating with the guanine nucleotide exchange factor (GEF) Vav. Rac stimulation in turn is critical for actin cytoskeleton rearrangements that generate lamellipodial protrusions and lead to bacterial uptake. Principal Findings: In our present study we provide biochemical and microscopic evidence that the adaptor proteins Nck1 and Nck2, but not CrkL, Grb2 or SLP-76, bind to tyrosine phosphorylated CEACAM3. The association is phosphorylation-dependent and requires the Nck SH2 domain. Overexpression of the isolated Nck1 SH2 domain, RNAi-mediated knock-down of Nck1, or genetic deletion of Nck1 and Nck2 interfere with CEACAM3-mediated bacterial internalization and with the formation of lamellipodial protrusions. Nck is constitutively associated with WAVE2 and directs the actin nucleation promoting WAVE complex to tyrosine phosphorylated CEACAM3. In turn, dominant-negative WAVE2 as well as shRNA-mediated knock-down of WAVE2 or the WAVE-complex component Nap1 reduce internalization of bacteria. Conclusions: Our results provide novel mechanistic insight into CEACAM3-initiated phagocytosis. We suggest that the CEACAM3 ITAM-like sequence is optimized to co-ordinate a minimal set of cellular factors needed to efficiently trigger actin-based lamellipodial protrusions and rapid pathogen engulfment.}, language = {en} } @article{ZoephelReiherRexeretal.2012, author = {Zoephel, Judith and Reiher, Wencke and Rexer, Karl-Heinz and Kahnt, J{\"o}rg and Wegener, Christian}, title = {Peptidomics of the Agriculturally Damaging Larval Stage of the Cabbage Root Fly Delia radicum (Diptera: Anthomyiidae)}, series = {PLoS One}, volume = {7}, journal = {PLoS One}, number = {7}, doi = {10.1371/journal.pone.0041543}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-131727}, pages = {e41543}, year = {2012}, abstract = {The larvae of the cabbage root fly induce serious damage to cultivated crops of the family Brassicaceae. We here report the biochemical characterisation of neuropeptides from the central nervous system and neurohemal organs, as well as regulatory peptides from enteroendocrine midgut cells of the cabbage maggot. By LC-MALDI-TOF/TOF and chemical labelling with 4-sulfophenyl isothiocyanate, 38 peptides could be identified, representing major insect peptide families: allatostatin A, allatostatin C, FMRFamide-like peptides, kinin, CAPA peptides, pyrokinins, sNPF, myosuppressin, corazonin, SIFamide, sulfakinins, tachykinins, NPLP1-peptides, adipokinetic hormone and CCHamide 1. We also report a new peptide (Yamide) which appears to be homolog to an amidated eclosion hormone-associated peptide in several Drosophila species. Immunocytochemical characterisation of the distribution of several classes of peptide-immunoreactive neurons and enteroendocrine cells shows a very similar but not identical peptide distribution to Drosophila. Since peptides regulate many vital physiological and behavioural processes such as moulting or feeding, our data may initiate the pharmacological testing and development of new specific peptide-based protection methods against the cabbage root fly and its larva.}, language = {en} } @article{SchwerkPapandreouSchuhmannetal.2012, author = {Schwerk, Christian and Papandreou, Thalia and Schuhmann, Daniel and Nickol, Laura and Borkowski, Julia and Steinmann, Ulrike and Quednau, Natascha and Stump, Carolin and Weiss, Christel and Berger, J{\"u}rgen and Wolburg, Hartwig and Claus, Heike and Vogel, Ulrich and Ishikawa, Hiroshi and Tenenbaum, Tobias and Schroten, Horst}, title = {Polar Invasion and Translocation of Neisseria meningitidis and Streptococcus suis in a Novel Human Model of the Blood-Cerebrospinal Fluid Barrier}, series = {PLoS One}, volume = {7}, journal = {PLoS One}, number = {1}, doi = {10.1371/journal.pone.0030069}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-131459}, pages = {e30069}, year = {2012}, abstract = {Acute bacterial meningitis is a life-threatening disease in humans. Discussed as entry sites for pathogens into the brain are the blood-brain and the blood-cerebrospinal fluid barrier (BCSFB). Although human brain microvascular endothelial cells (HBMEC) constitute a well established human in vitro model for the blood-brain barrier, until now no reliable human system presenting the BCSFB has been developed. Here, we describe for the first time a functional human BCSFB model based on human choroid plexus papilloma cells (HIBCPP), which display typical hallmarks of a BCSFB as the expression of junctional proteins and formation of tight junctions, a high electrical resistance and minimal levels of macromolecular flux when grown on transwell filters. Importantly, when challenged with the zoonotic pathogen Streptococcus suis or the human pathogenic bacterium Neisseria meningitidis the HIBCPP show polar bacterial invasion only from the physiologically relevant basolateral side. Meningococcal invasion is attenuated by the presence of a capsule and translocated N. meningitidis form microcolonies on the apical side of HIBCPP opposite of sites of entry. As a functionally relevant human model of the BCSFB the HIBCPP offer a wide range of options for analysis of disease-related mechanisms at the choroid plexus epithelium, especially involving human pathogens.}, language = {en} } @article{GassenBrechtefeldSchandryetal.2012, author = {Gassen, Alwine and Brechtefeld, Doris and Schandry, Niklas and Arteaga-Salas, J. Manuel and Israel, Lars and Imhof, Axel and Janzen, Christian J.}, title = {DOT1A-dependent H3K76 methylation is required for replication regulation in Trypanosoma brucei}, series = {Nucleic Acids Research}, volume = {40}, journal = {Nucleic Acids Research}, number = {20}, doi = {10.1093/nar/gks801}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-131449}, pages = {10302 - 10311}, year = {2012}, abstract = {Cell-cycle progression requires careful regulation to ensure accurate propagation of genetic material to the daughter cells. Although many cell-cycle regulators are evolutionarily conserved in the protozoan parasite Trypanosoma brucei, novel regulatory mechanisms seem to have evolved. Here, we analyse the function of the histone methyltransferase DOT1A during cell-cycle progression. Over-expression of DOT1A generates a population of cells with aneuploid nuclei as well as enucleated cells. Detailed analysis shows that DOT1A over-expression causes continuous replication of the nuclear DNA. In contrast, depletion of DOT1A by RNAi abolishes replication but does not prevent karyokinesis. As histone H3K76 methylation has never been associated with replication control in eukaryotes before, we have discovered a novel function of DOT1 enzymes, which might not be unique to trypanosomes.}, language = {en} } @article{HafnerHoubenBaeurleetal.2012, author = {Hafner, Christian and Houben, Roland and Baeurle, Anne and Ritter, Cathrin and Schrama, David and Landthaler, Michael and Becker, J{\"u}rgen C.}, title = {Activation of the PI3K/AKT Pathway in Merkel Cell Carcinoma}, series = {PLoS One}, volume = {7}, journal = {PLoS One}, number = {2}, doi = {10.1371/journal.pone.0031255}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-131398}, pages = {e31255}, year = {2012}, abstract = {Merkel cell carcinoma (MCC) is a highly aggressive skin cancer with an increasing incidence. The understanding of the molecular carcinogenesis of MCC is limited. Here, we scrutinized the PI3K/AKT pathway, one of the major pathways activated in human cancer, in MCC. Immunohistochemical analysis of 41 tumor tissues and 9 MCC cell lines revealed high levels of AKT phosphorylation at threonine 308 in 88\% of samples. Notably, the AKT phosphorylation was not correlated with the presence or absence of the Merkel cell polyoma virus (MCV). Accordingly, knock-down of the large and small T antigen by shRNA in MCV positive MCC cells did not affect phosphorylation of AKT. We also analyzed 46 MCC samples for activating PIK3CA and AKT1 mutations. Oncogenic PIK3CA mutations were found in 2/46 (4\%) MCCs whereas mutations in exon 4 of AKT1 were absent. MCC cell lines demonstrated a high sensitivity towards the PI3K inhibitor LY-294002. This finding together with our observation that the PI3K/AKT pathway is activated in the majority of human MCCs identifies PI3K/AKT as a potential new therapeutic target for MCC patients.}, language = {en} } @article{vanKoolwijkRamdasIkrametal.2012, author = {van Koolwijk, Leonieke M. E. and Ramdas, Wishal D. and Ikram, M. Kamran and Jansonius, Nomdo M. and Pasutto, Francesca and Hys, Pirro G. and Macgregor, Stuart and Janssen, Sarah F. and Hewitt, Alex W. and Viswanathan, Ananth C. and ten Brink, Jacoline B. and Hosseini, S. Mohsen and Amin, Najaf and Despriet, Dominiek D. G. and Willemse-Assink, Jacqueline J. M. and Kramer, Rogier and Rivadeneira, Fernando and Struchalin, Maksim and Aulchenko, Yurii S. and Weisschuh, Nicole and Zenkel, Matthias and Mardin, Christian Y. and Gramer, Eugen and Welge-L{\"u}ssen, Ulrich and Montgomery, Grant W. and Carbonaro, Francis and Young, Terri L. and Bellenguez, C{\´e}line and McGuffin, Peter and Foster, Paul J. and Topouzis, Fotis and Mitchell, Paul and Wang, Jie Jin and Wong, Tien Y. and Czudowska, Monika A. and Hofman, Albert and Uitterlinden, Andre G. and Wolfs, Roger C. W. and de Jong, Paulus T. V. M. and Oostra, Ben A. and Paterson, Andrew D. and Mackey, David A. and Bergen, Arthur A. B. and Reis, Andre and Hammond, Christopher J. and Vingerling, Johannes R. and Lemij, Hans G. and Klaver, Caroline C. W. and van Duijn, Cornelia M.}, title = {Common Genetic Determinants of Intraocular Pressure and Primary Open-Angle Glaucoma}, series = {PLoS Genetics}, volume = {8}, journal = {PLoS Genetics}, number = {5}, doi = {10.1371/journal.pgen.1002611}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-131378}, pages = {e1002611}, year = {2012}, abstract = {Intraocular pressure (IOP) is a highly heritable risk factor for primary open-angle glaucoma and is the only target for current glaucoma therapy. The genetic factors which determine IOP are largely unknown. We performed a genome-wide association study for IOP in 11,972 participants from 4 independent population-based studies in The Netherlands. We replicated our findings in 7,482 participants from 4 additional cohorts from the UK, Australia, Canada, and the Wellcome Trust Case-Control Consortium 2/Blue Mountains Eye Study. IOP was significantly associated with rs11656696, located in GAS7 at 17p13.1 (p = 1.4 x 10\(^{-8}\)), and with rs7555523, located in TMCO1 at 1q24.1 (p = 1.6 x 10\(^{-8}\)). In a meta-analysis of 4 case-control studies (total N = 1,432 glaucoma cases), both variants also showed evidence for association with glaucoma (p = 2.4 x 10\(^{-2}\) for rs11656696 and p = 9.1 x 10\(^{-4}\) for rs7555523). GAS7 and TMCO1 are highly expressed in the ciliary body and trabecular meshwork as well as in the lamina cribrosa, optic nerve, and retina. Both genes functionally interact with known glaucoma disease genes. These data suggest that we have identified two clinically relevant genes involved in IOP regulation.}, language = {en} } @article{StaigerCadotKooteretal.2012, author = {Staiger, Christine and Cadot, Sidney and Kooter, Raul and Dittrich, Marcus and M{\"u}ller, Tobias and Klau, Gunnar W. and Wessels, Lodewyk F. A.}, title = {A Critical Evaluation of Network and Pathway-Based Classifiers for Outcome Prediction in Breast Cancer}, series = {PLoS One}, volume = {7}, journal = {PLoS One}, number = {4}, doi = {10.1371/journal.pone.0034796}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-131323}, pages = {e34796}, year = {2012}, abstract = {Recently, several classifiers that combine primary tumor data, like gene expression data, and secondary data sources, such as protein-protein interaction networks, have been proposed for predicting outcome in breast cancer. In these approaches, new composite features are typically constructed by aggregating the expression levels of several genes. The secondary data sources are employed to guide this aggregation. Although many studies claim that these approaches improve classification performance over single genes classifiers, the gain in performance is difficult to assess. This stems mainly from the fact that different breast cancer data sets and validation procedures are employed to assess the performance. Here we address these issues by employing a large cohort of six breast cancer data sets as benchmark set and by performing an unbiased evaluation of the classification accuracies of the different approaches. Contrary to previous claims, we find that composite feature classifiers do not outperform simple single genes classifiers. We investigate the effect of (1) the number of selected features; (2) the specific gene set from which features are selected; (3) the size of the training set and (4) the heterogeneity of the data set on the performance of composite feature and single genes classifiers. Strikingly, we find that randomization of secondary data sources, which destroys all biological information in these sources, does not result in a deterioration in performance of composite feature classifiers. Finally, we show that when a proper correction for gene set size is performed, the stability of single genes sets is similar to the stability of composite feature sets. Based on these results there is currently no reason to prefer prognostic classifiers based on composite features over single genes classifiers for predicting outcome in breast cancer.}, language = {en} } @article{GrassmannFritscheKeilhaueretal.2012, author = {Grassmann, Felix and Fritsche, Lars G. and Keilhauer, Claudia N. and Heid, Iris M. and Weber, Bernhard H. F.}, title = {Modelling the Genetic Risk in Age-Related Macular Degeneration}, series = {PLoS One}, volume = {7}, journal = {PLoS One}, number = {5}, doi = {10.1371/journal.pone.0037979}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-131315}, pages = {e37979}, year = {2012}, abstract = {Late-stage age-related macular degeneration (AMD) is a common sight-threatening disease of the central retina affecting approximately 1 in 30 Caucasians. Besides age and smoking, genetic variants from several gene loci have reproducibly been associated with this condition and likely explain a large proportion of disease. Here, we developed a genetic risk score (GRS) for AMD based on 13 risk variants from eight gene loci. The model exhibited good discriminative accuracy, area-under-curve (AUC) of the receiver-operating characteristic of 0.820, which was confirmed in a cross-validation approach. Noteworthy, younger AMD patients aged below 75 had a significantly higher mean GRS (1.87, 95\% CI: 1.69-2.05) than patients aged 75 and above (1.45, 95\% CI: 1.36-1.54). Based on five equally sized GRS intervals, we present a risk classification with a relative AMD risk of 64.0 (95\% CI: 14.11-1131.96) for individuals in the highest category (GRS 3.44-5.18, 0.5\% of the general population) compared to subjects with the most common genetic background (GRS -0.05-1.70, 40.2\% of general population). The highest GRS category identifies AMD patients with a sensitivity of 7.9\% and a specificity of 99.9\% when compared to the four lower categories. Modeling a general population around 85 years of age, 87.4\% of individuals in the highest GRS category would be expected to develop AMD by that age. In contrast, only 2.2\% of individuals in the two lowest GRS categories which represent almost 50\% of the general population are expected to manifest AMD. Our findings underscore the large proportion of AMD cases explained by genetics particularly for younger AMD patients. The five-category risk classification could be useful for therapeutic stratification or for diagnostic testing purposes once preventive treatment is available.}, language = {en} } @article{JainJavdanFegeretal.2012, author = {Jain, Preetesh and Javdan, Mohammad and Feger, Franziska K. and Chiu, Pui Yan and Sison, Cristina and Damle, Rajendra N. and Bhuiya, Tawfiqul A. and Sen, Filiz and Abruzzo, Lynne V. and Burger, Jan A. and Rosenwald, Andreas and Allen, Steven L. and Kolitz, Jonathan E. and Rai, Kanti R. and Chiorazzi, Nicholas and Sherry, Barbara}, title = {Th17 and non-Th17 interleukin-17-expressing cells in chronic lymphocytic leukemia: delineation, distribution, and clinical relevance}, series = {Haematologica}, volume = {97}, journal = {Haematologica}, number = {4}, doi = {10.3324/haematol.2011.047316}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-131290}, pages = {599 - 607}, year = {2012}, abstract = {Background The levels and clinical relevance of Th17 cells and other interleukin-17-producing cells have not been analyzed in chronic lymphocytic leukemia. The objective of this study was to quantify blood and tissue levels of Th17 and other interleukin-17-producing cells in patients with this disease and correlate blood levels with clinical outcome. Design and Methods: Intracellular interleukin-17A was assessed in blood and splenic mononuclear cells from patients with chronic lymphocytic leukemia and healthy subjects using flow cytometry. Interleukin-17A-producing cells were analyzed in formalin-fixed, paraffin-embedded spleen and lymph node sections using immunohistochemistry and immunofluorescence. Results: The absolute numbers of Th17 cells in peripheral blood mononuclear cells and the percentages of Th17 cells in spleen cell suspensions were higher in patients with chronic lymphocytic leukemia than in healthy subjects; in six out of eight paired chronic lymphocytic leukemia blood and spleen sample comparisons, Th17 cells were enriched in spleen suspensions. Circulating Th17 levels correlated with better prognostic markers and longer overall survival of the patients. Two "non-Th17" interleukin-17-expressing cells were identified in chronic lymphocytic leukemia spleens: proliferating cells of the granulocytic lineage and mature mast cells. Granulocytes and mast cells in normal spleens did not express interleukin-17. Conversely, both chronic lymphocytic leukemia and healthy lymph nodes contained similar numbers of interleukin-17+ mast cells as well as Th17 cells. Conclusions: Th17 cells are elevated in chronic lymphocytic leukemia patients with better prognostic markers and correlate with longer survival. Furthermore, non-Th17 interleukin-17A-expressing cells exist in chronic lymphocytic leukemia spleens as maturing granulocytes and mature mast cells, suggesting that the microenvironmental milieu in leukemic spleens promotes the recruitment and/or expansion of Th17 and other IL-17-expressing cells. The pathophysiology of Th17 and non-Th17-interleukin-producing cells in chronic lymphocytic leukemia and their distributions and roles in this disease merit further study.}, language = {en} } @article{BoehlerCreignouGalotaetal.2012, author = {B{\"o}hler, Elmar and Creignou, Nadia and Galota, Matthias and Reith, Steffen and Schnoor, Henning and Vollmer, Heribert}, title = {Complexity Classifications for Different Equivalence and Audit Problems for Boolean Circuits}, series = {Logical Methods in Computer Science}, volume = {8}, journal = {Logical Methods in Computer Science}, number = {3:27}, doi = {10.2168/LMCS-8(3:27)2012}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-131121}, pages = {1 -- 25}, year = {2012}, abstract = {We study Boolean circuits as a representation of Boolean functions and conskier different equivalence, audit, and enumeration problems. For a number of restricted sets of gate types (bases) we obtain efficient algorithms, while for all other gate types we show these problems are at least NP-hard.}, language = {en} } @article{HofgaardJodalBommertetal.2012, author = {Hofgaard, Peter O. and Jodal, Henriette C. and Bommert, Kurt and Huard, Bertrand and Caers, Jo and Carlsen, Harald and Schwarzer, Rolf and Sch{\"u}nemann, Nicole and Jundt, Franziska and Lindeberg, Mona M. and Bogen, Bjarne}, title = {A Novel Mouse Model for Multiple Myeloma (MOPC315.BM) That Allows Noninvasive Spatiotemporal Detection of Osteolytic Disease}, series = {PLoS One}, volume = {7}, journal = {PLoS One}, number = {12}, doi = {10.1371/journal.pone.0051892}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-131117}, pages = {e51892}, year = {2012}, abstract = {Multiple myeloma (MM) is a lethal human cancer characterized by a clonal expansion of malignant plasma cells in bone marrow. Mouse models of human MM are technically challenging and do not always recapitulate human disease. Therefore, new mouse models for MM are needed. Mineral-oil induced plasmacytomas (MOPC) develop in the peritoneal cavity of oil-injected BALB/c mice. However, MOPC typically grow extramedullary and are considered poor models of human MM. Here we describe an in vivo-selected MOPC315 variant, called MOPC315.BM, which can be maintained in vitro. When injected i.v. into BALB/c mice, MOPC315.BM cells exhibit tropism for bone marrow. As few as 10\(^4\) MOPC315.BM cells injected i.v. induced paraplegia, a sign of spinal cord compression, in all mice within 3-4 weeks. MOPC315.BM cells were stably transfected with either firefly luciferase (MOPC315.BM.Luc) or DsRed (MOPC315.BM.DsRed) for studies using noninvasive imaging. MOPC315.BM.Luc cells were detected in the tibiofemoral region already 1 hour after i.v. injection. Bone foci developed progressively, and as of day 5, MM cells were detected in multiple sites in the axial skeleton. Additionally, the spleen (a hematopoietic organ in the mouse) was invariably affected. Luminescent signals correlated with serum myeloma protein concentration, allowing for easy tracking of tumor load with noninvasive imaging. Affected mice developed osteolytic lesions. The MOPC315.BM model employs a common strain of immunocompetent mice (BALB/c) and replicates many characteristics of human MM. The model should be suitable for studies of bone marrow tropism, development of osteolytic lesions, drug testing, and immunotherapy in MM.}, language = {en} } @article{MessiNdjokoIosetHertleinAmslingeretal.2012, author = {Messi, Bernadette Biloa and Ndjoko-Ioset, Karine and Hertlein-Amslinger, Barbara and Lannang, Alain Meli and Nkengfack, Augustin E. and Wolfender, Jean-Luc and Hostettmann, Kurt and Bringmann, Gerhard}, title = {Preussianone, a New Flavanone-Chromone Biflavonoid from Garcinia preussii Engl.}, series = {Molecules}, volume = {17}, journal = {Molecules}, number = {5}, doi = {10.3390/molecules17056114}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-130881}, pages = {6114 - 6125}, year = {2012}, abstract = {A new flavanone-chromone biflavonoid, preussianone (1), has been isolated from the leaves of Garcinia preussii, along with four known biflavonoids. The absolute stereostructures were elucidated by chemical, spectroscopic, and chiroptical methods. The biological properties of the new biflavonoid against several bacterial strains were evaluated.}, language = {en} } @article{BetzSchneiderKressetal.2012, author = {Betz, Boris and Schneider, Reinhard and Kress, Tobias and Schick, Martin Alexander and Wanner, Christoph and Sauvant, Christoph}, title = {Rosiglitazone Affects Nitric Oxide Synthases and Improves Renal Outcome in a Rat Model of Severe Ischemia/Reperfusion Injury}, series = {PPAR Research}, volume = {2012}, journal = {PPAR Research}, number = {Article ID 219319}, doi = {10.1155/2012/219319}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-130872}, pages = {12}, year = {2012}, abstract = {Background. Nitric oxide (NO)-signal transduction plays an important role in renal ischemia/reperfusion (I/R) injury. NO produced by endothelial NO-synthase (eNOS) has protective functions whereas NO from inducible NO-synthase (iNOS) induces impairment. Rosiglitazone (RGZ), a peroxisome proliferator-activated receptor (PPAR)-gamma agonist exerted beneficial effects after renal I/R injury, so we investigated whether this might be causally linked with NOS imbalance. Methods. RGZ (5 mg/kg) was administered i.p. to SD-rats (f) subjected to bilateral renal ischemia (60 min). Following 24 h of reperfusion, inulin-and PAH-clearance as well as PAH-net secretion were determined. Morphological alterations were graded by histopathological scoring. Plasma NOx-production was measured. eNOS and iNOS expression was analyzed by qPCR. Cleaved caspase 3 (CC3) was determined as an apoptosis indicator and ED1 as a marker of macrophage infiltration in renal tissue. Results. RGZ improves renal function after renal I/R injury (PAH-/inulin-clearance, PAH-net secretion) and reduces histomorphological injury. Additionally, RGZ reduces NOx plasma levels, ED-1 positive cell infiltration and CC3 expression. iNOS-mRNA is reduced whereas eNOS-mRNA is increased by RGZ. Conclusion. RGZ has protective properties after severe renal I/R injury. Alterations of the NO pathway regarding eNOS and iNOS could be an explanation of the underlying mechanism of RGZ protection in renal I/R injury.}, language = {en} } @article{ElKeredySchleyerKoenigetal.2012, author = {El-Keredy, Amira and Schleyer, Michael and K{\"o}nig, Christian and Ekim, Aslihan and Gerber, Bertram}, title = {Behavioural Analyses of Quinine Processing in Choice, Feeding and Learning of Larval Drosophila}, series = {PLoS One}, volume = {7}, journal = {PLoS One}, number = {7}, doi = {10.1371/journal.pone.0040525}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-130811}, pages = {e40525}, year = {2012}, abstract = {Gustatory stimuli can support both immediate reflexive behaviour, such as choice and feeding, and can drive internal reinforcement in associative learning. For larval Drosophila, we here provide a first systematic behavioural analysis of these functions with respect to quinine as a study case of a substance which humans report as "tasting bitter". We describe the dose-effect functions for these different kinds of behaviour and find that a half-maximal effect of quinine to suppress feeding needs substantially higher quinine concentrations (2.0 mM) than is the case for internal reinforcement (0.6 mM). Interestingly, in previous studies (Niewalda et al. 2008, Schipanski et al 2008) we had found the reverse for sodium chloride and fructose/sucrose, such that dose-effect functions for those tastants were shifted towards lower concentrations for feeding as compared to reinforcement, arguing that the differences in dose-effect function between these behaviours do not reflect artefacts of the types of assay used. The current results regarding quinine thus provide a starting point to investigate how the gustatory system is organized on the cellular and/or molecular level to result in different behavioural tuning curves towards a bitter tastant.}, language = {en} } @article{BauneKonradGrotegerdetal.2012, author = {Baune, Bernhard T. and Konrad, Carsten and Grotegerd, Dominik and Suslow, Thomas and Birosova, Eva and Ohrmann, Patricia and Bauer, Jochen and Arolt, Volker and Heindel, Walter and Domschke, Katharina and Sch{\"o}ning, Sonja and Rauch, Astrid V. and Uhlmann, Christina and Kugel, Harald and Dannlowski, Udo}, title = {Interleukin-6 gene (IL-6): a possible role in brain morphology in the healthy adult brain}, series = {Journal of Neuroinflammation}, volume = {9}, journal = {Journal of Neuroinflammation}, number = {125}, doi = {10.1186/1742-2094-9-125}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-130804}, year = {2012}, abstract = {Background: Cytokines such as interleukin 6 (IL-6) have been implicated in dual functions in neuropsychiatric disorders. Little is known about the genetic predisposition to neurodegenerative and neuroproliferative properties of cytokine genes. In this study the potential dual role of several IL-6 polymorphisms in brain morphology is investigated. Methodology: In a large sample of healthy individuals (N = 303), associations between genetic variants of IL-6 (rs1800795; rs1800796, rs2069833, rs2069840) and brain volume (gray matter volume) were analyzed using voxel-based morphometry (VBM). Selection of single nucleotide polymorphisms (SNPs) followed a tagging SNP approach (e. g., Stampa algorigthm), yielding a capture 97.08\% of the variation in the IL-6 gene using four tagging SNPs. Principal findings/results In a whole-brain analysis, the polymorphism rs1800795 (-174 C/G) showed a strong main effect of genotype (43 CC vs. 150 CG vs. 100 GG; x = 24, y = -10, z = -15; F(2,286) = 8.54, p(uncorrected) = 0.0002; p(AlphaSim-corrected) = 0.002; cluster size k = 577) within the right hippocampus head. Homozygous carriers of the G-allele had significantly larger hippocampus gray matter volumes compared to heterozygous subjects. None of the other investigated SNPs showed a significant association with grey matter volume in whole-brain analyses. Conclusions/significance: These findings suggest a possible neuroprotective role of the G-allele of the SNP rs1800795 on hippocampal volumes. Studies on the role of this SNP in psychiatric populations and especially in those with an affected hippocampus (e.g., by maltreatment, stress) are warranted.}, language = {en} } @article{HerbertMuthPollatosetal.2012, author = {Herbert, Beate M. and Muth, Eric R. and Pollatos, Olga and Herbert, Cornelia}, title = {Interoception across Modalities: On the Relationship between Cardiac Awareness and the Sensitivity for Gastric Functions}, series = {PLoS One}, volume = {7}, journal = {PLoS One}, number = {5}, doi = {10.1371/journal.pone.0036646}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-130733}, pages = {e36646}, year = {2012}, abstract = {The individual sensitivity for ones internal bodily signals ("interoceptive awareness") has been shown to be of relevance for a broad range of cognitive and affective functions. Interoceptive awareness has been primarily assessed via measuring the sensitivity for ones cardiac signals ("cardiac awareness") which can be non-invasively measured by heartbeat perception tasks. It is an open question whether cardiac awareness is related to the sensitivity for other bodily, visceral functions. This study investigated the relationship between cardiac awareness and the sensitivity for gastric functions in healthy female persons by using non-invasive methods. Heartbeat perception as a measure for cardiac awareness was assessed by a heartbeat tracking task and gastric sensitivity was assessed by a water load test. Gastric myoelectrical activity was measured by electrogastrography (EGG) and subjective feelings of fullness, valence, arousal and nausea were assessed. The results show that cardiac awareness was inversely correlated with ingested water volume and with normogastric activity after water load. However, persons with good and poor cardiac awareness did not differ in their subjective ratings of fullness, nausea and affective feelings after drinking. This suggests that good heartbeat perceivers ingested less water because they subjectively felt more intense signals of fullness during this lower amount of water intake compared to poor heartbeat perceivers who ingested more water until feeling the same signs of fullness. These findings demonstrate that cardiac awareness is related to greater sensitivity for gastric functions, suggesting that there is a general sensitivity for interoceptive processes across the gastric and cardiac modality.}, language = {en} } @article{WillemsUrlichsSeidenspinneretal.2012, author = {Willems, Coen H. M. P. and Urlichs, Florian and Seidenspinner, Silvia and Kunzmann, Steffen and Speer, Christian P. and Kramer, Boris W.}, title = {Poractant alfa (Curosurf (R)) increases phagocytosis of apoptotic neutrophils by alveolar macrophages in vivo}, series = {Respiratory Research}, volume = {13}, journal = {Respiratory Research}, number = {17}, doi = {10.1186/1465-9921-13-17}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-130721}, year = {2012}, abstract = {Background: Clearance of apoptotic neutrophils in the lung is an essential process to limit inflammation, since they could become a pro-inflammatory stimulus themselves. The clearance is partially mediated by alveolar macrophages, which phagocytose these apoptotic cells. The phagocytosis of apoptotic immune cells by monocytes in vitro has been shown to be augmented by several constituents of pulmonary surfactant, e. g. phospholipids and hydrophobic surfactant proteins. In this study, we assessed the influence of exogenous poractant alfa (Curosurf (R)) instillation on the in vivo phagocytosis of apoptotic neutrophils by alveolar macrophages. Methods: Poractant alfa (200 mg/kg) was instilled intratracheally in the lungs of three months old adult male C57/Black 6 mice, followed by apoptotic neutrophil instillation. Bronchoalveloar lavage was performed and alveolar macrophages and neutrophils were counted. Phagocytosis of apoptotic neutrophils was quantified by determining the number of apoptotic neutrophils per alveolar macrophages. Results: Exogenous surfactant increased the number of alveolar macrophages engulfing apoptotic neutrophils 2.6 fold. The phagocytosis of apoptotic neutrophils was increased in the presence of exogenous surfactant by a 4.7 fold increase in phagocytosed apoptotic neutrophils per alveolar macrophage. Conclusions: We conclude that the anti-inflammatory properties of surfactant therapy may be mediated in part by increased numbers of alveolar macrophages and increased phagocytosis of apoptotic neutrophils by alveolar macrophages.}, language = {en} } @article{WeisseHeddergottHeydtetal.2012, author = {Weiße, Sebastian and Heddergott, Niko and Heydt, Matthias and Pfl{\"a}sterer, Daniel and Maier, Timo and Haraszti, Tamas and Grunze, Michael and Engstler, Markus and Rosenhahn, Axel}, title = {A Quantitative 3D Motility Analysis of Trypanosoma brucei by Use of Digital In-line Holographic Microscopy}, series = {PLoS One}, volume = {7}, journal = {PLoS One}, number = {5}, doi = {10.1371/journal.pone.0037296}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-130666}, pages = {e37296}, year = {2012}, abstract = {We present a quantitative 3D analysis of the motility of the blood parasite Trypanosoma brucei. Digital in-line holographic microscopy has been used to track single cells with high temporal and spatial accuracy to obtain quantitative data on their behavior. Comparing bloodstream form and insect form trypanosomes as well as mutant and wildtype cells under varying external conditions we were able to derive a general two-state-run-and-tumble-model for trypanosome motility. Differences in the motility of distinct strains indicate that adaption of the trypanosomes to their natural environments involves a change in their mode of swimming.}, language = {en} } @article{BugaScholzKumaretal.2012, author = {Buga, Ana-Maria and Scholz, Claus J{\"u}rgen and Kumar, Senthil and Herndon, James G. and Alexandru, Dragos and Cojocaru, Gabriel Radu and Dandekar, Thomas and Popa-Wagner, Aurel}, title = {Identification of New Therapeutic Targets by Genome-Wide Analysis of Gene Expression in the Ipsilateral Cortex of Aged Rats after Stroke}, series = {PLoS One}, volume = {7}, journal = {PLoS One}, number = {12}, doi = {10.1371/journal.pone.0050985}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-130657}, pages = {e50985}, year = {2012}, abstract = {Background: Because most human stroke victims are elderly, studies of experimental stroke in the aged rather than the young rat model may be optimal for identifying clinically relevant cellular responses, as well for pinpointing beneficial interventions. Methodology/Principal Findings: We employed the Affymetrix platform to analyze the whole-gene transcriptome following temporary ligation of the middle cerebral artery in aged and young rats. The correspondence, heat map, and dendrogram analyses independently suggest a differential, age-group-specific behaviour of major gene clusters after stroke. Overall, the pattern of gene expression strongly suggests that the response of the aged rat brain is qualitatively rather than quantitatively different from the young, i.e. the total number of regulated genes is comparable in the two age groups, but the aged rats had great difficulty in mounting a timely response to stroke. Our study indicates that four genes related to neuropathic syndrome, stress, anxiety disorders and depression (Acvr1c, Cort, Htr2b and Pnoc) may have impaired response to stroke in aged rats. New therapeutic options in aged rats may also include Calcrl, Cyp11b1, Prcp, Cebpa, Cfd, Gpnmb, Fcgr2b, Fcgr3a, Tnfrsf26, Adam 17 and Mmp14. An unexpected target is the enzyme 3-hydroxy-3-methylglutaryl-Coenzyme A synthase 1 in aged rats, a key enzyme in the cholesterol synthesis pathway. Post-stroke axonal growth was compromised in both age groups. Conclusion/Significance: We suggest that a multi-stage, multimodal treatment in aged animals may be more likely to produce positive results. Such a therapeutic approach should be focused on tissue restoration but should also address other aspects of patient post-stroke therapy such as neuropathic syndrome, stress, anxiety disorders, depression, neurotransmission and blood pressure.}, language = {en} }