TY - JOUR A1 - Bousquet, J. A1 - Anto, J. M. A1 - Akdis, M. A1 - Auffray, C. A1 - Keil, T. A1 - Momas, I. A1 - Postma, D. S. A1 - Valenta, R. A1 - Wickman, M. A1 - Cambon-Thomsen, A. A1 - Haahtela, T. A1 - Lambrecht, B. N. A1 - Lodrup Carlsen, K. C. A1 - Koppelman, G. H. A1 - Sunyer, J. A1 - Zuberbier, T. A1 - Annesi-Maesano, I. A1 - Arno, A. A1 - Bindslev-Jensen, C. A1 - De Carlo, G. A1 - Forastiere, F. A1 - Heinrich, J. A1 - Kowalski, M. L. A1 - Maier, D. A1 - Melen, E. A1 - Palkonen, S. A1 - Smit, H. A. A1 - Standl, M. A1 - Wright, J. A1 - Asarnoj, A. A1 - Benet, M. A1 - Ballardini, N. A1 - Garcia-Aymerich, J. A1 - Gehring, U. A1 - Guerra, S. A1 - Hohman, C. A1 - Kull, I. A1 - Lupinek, C. A1 - Pinart, M. A1 - Skrindo, I. A1 - Westman, M. A1 - Smagghe, D. A1 - Akdis, C. A1 - Albang, R. A1 - Anastasova, V. A1 - Anderson, N. A1 - Bachert, C. A1 - Ballereau, S. A1 - Ballester, F. A1 - Basagana, X. A1 - Bedbrook, A. A1 - Bergstrom, A. A1 - von Berg, A. A1 - Brunekreef, B. A1 - Burte, E. A1 - Carlsen, K.H. A1 - Chatzi, L. A1 - Coquet, J.M. A1 - Curin, M. A1 - Demoly, P. A1 - Eller, E. A1 - Fantini, M.P. A1 - Gerhard, B. A1 - Hammad, H. A1 - von Hertzen, L. A1 - Hovland, V. A1 - Jacquemin, B. A1 - Just, J. A1 - Keller, T. A1 - Kerkhof, M. A1 - Kiss, R. A1 - Kogevinas, M. A1 - Koletzko, S. A1 - Lau, S. A1 - Lehmann, I. A1 - Lemonnier, N. A1 - McEachan, R. A1 - Makela, M. A1 - Mestres, J. A1 - Minina, E. A1 - Mowinckel, P. A1 - Nadif, R. A1 - Nawijn, M. A1 - Oddie, S. A1 - Pellet, J. A1 - Pin, I. A1 - Porta, D. A1 - Rancière, F. A1 - Rial-Sebbag, A. A1 - Schuijs, M.J. A1 - Siroux, V. A1 - Tischer, C.G. A1 - Torrent, M. A1 - Varraso, R. A1 - De Vocht, J. A1 - Wenger, K. A1 - Wieser, S. A1 - Xu, C. T1 - Paving the way of systems biology and precision medicine in allergic diseases: the MeDALL success story Mechanisms of the Development of ALLergy; EUFP7-CP-IP; Project No: 261357; 2010-2015 JF - Allergy N2 - MeDALL (Mechanisms of the Development of ALLergy; EU FP7-CP-IP; Project No: 261357; 2010-2015) has proposed an innovative approach to develop early indicators for the prediction, diagnosis, prevention and targets for therapy. MeDALL has linked epidemiological, clinical and basic research using a stepwise, large-scale and integrative approach: MeDALL data of precisely phenotyped children followed in 14 birth cohorts spread across Europe were combined with systems biology (omics, IgE measurement using microarrays) and environmental data. Multimorbidity in the same child is more common than expected by chance alone, suggesting that these diseases share causal mechanisms irrespective of IgE sensitization. IgE sensitization should be considered differently in monosensitized and polysensitized individuals. Allergic multimorbidities and IgE polysensitization are often associated with the persistence or severity of allergic diseases. Environmental exposures are relevant for the development of allergy-related diseases. To complement the population-based studies in children, MeDALL included mechanistic experimental animal studies and in vitro studies in humans. The integration of multimorbidities and polysensitization has resulted in a new classification framework of allergic diseases that could help to improve the understanding of genetic and epigenetic mechanisms of allergy as well as to better manage allergic diseases. Ethics and gender were considered. MeDALL has deployed translational activities within the EU agenda. KW - asthma KW - birth cohort KW - atopic-dermatitis KW - immune-responses KW - IgE KW - multimorbidity KW - polysensitization KW - rhinitis KW - chronic respiratory-diseases KW - childhood asthma KW - immunological reactivity KW - IgE sensitazion KW - immunoglobulin-e KW - integraed care Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-186858 VL - 71 IS - 11 ER - TY - JOUR A1 - Xu, K. A1 - Näveri, L. A1 - Frerichs, K. A1 - Hallenbeck, J. M. A1 - Feuerstein, G. A1 - Davis, J. N. A1 - Sirén, Anna-Leena T1 - Extracellular catecholamine levels in rat hippocampus after a selective alpha2-adrenoceptor antagonist or a selective dopamnie uptake inhibitor: Evidence for dopamine release from local dopaminergic nerve terminals N2 - The effect of 6-chloro-2,3,4,5-tetrahydro-3-methyi-1-H-3-benzazepine (SKF 86466), a selectlve nonimldazoline alpha-2 adrenoceptor antagonlst, on hippocampal re1ease of norepinephrine and dopamlne in conscious rats was lnvestigated by /n vlvo mlcrodialysis and high-pressure liquid chromatography. Additionally, extracellular concentrations of hippocampal dopamine (DA) and norepinephrtne (NE), durtng Infusion of selective monoamine uptake Inhibitors, were determined in freely moving rats. The basal concentration of NE in the dialysate was 4.9 ± 0.3 pg/20 pl. lntravenous admlnistratlon of 5 or 10 mgJkg of SKF 86466 was associated wlth a transierlt inc:rease (30 min) of 2-fold (12 ± 1 pg/20 ,d; p < .05) and 8-fold (39 ± 3 pg/20 pl; p < .05), respectlvely, in dlalysate NE, whereas a 1-mgfkg dose had no effect. DA was not detected in basal dlalysates, but after the adminlstratlon of 5 or 10 mgJkg of SKF 86466, 3.9 ± 0.4 and 6.4 ± 0.6 pg/20 pl, respectlvely, was present in the dialysates. The rnaxlmum increase in dialysate DA was reached 60 to 90 min after SKF 86466. The DA was not derived from plasma because plasma NE was elevated after the 5 mgJkg dose of SKF 86466 whereas no plasma DA was detected. ln order to determlne whether DA was present in noradrenergic nerve termlnals, the dopamine ß-hydroxylase Inhibitor SKF 1 02698 was administered (50 mgJkg i.p.). The Inhibitor decreased dialysate NE but DA was stin not detected in the dialysate. When SKF 86466 (5 mgJkg t.v.) was adminlstered 4 hr after SKF 102698, DA appeared in the dialysate but there was no lncrease in dialysate NE. Administration through the dialysis probe of the DA uptake Inhibitor, GBR-12909 (0.1 and 1 pM), dose-dependently lnaeased DA Ieveis to 5.7 ± 1.2 and 9.6 ± 2.8 pg/20 pl, respectively. GBR-12909 had no effect on hippocampal NE. Desipramine (5 and 10 pM) lncreased dose-dependently dialysate NE and lncreased DA concentrations to detectable Ieveis (2.7 ± 0.5 and 3.5 ± 0.7 pg/20 ,d, respectively). These results suggest that the a/pha-2 adrenoceptors modulate both NE and DA release in the rat hlppocampus and that DA detected in the hlppocampal dialysate might be released from dopaminergic neurons. KW - Neurobiologie Y1 - 1993 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-62997 ER - TY - JOUR A1 - Shuaib, A. A1 - Xu, K. A1 - Crain, B. A1 - Sirén, Anna-Leena A1 - Feuerstein, Giora A1 - Hallenbeck, J. A1 - Davis, JN T1 - Assessment of damage from implantation of microdialysis probes in the rat hippocampus with silver degeneration staining N2 - We used a sensitive silver degeneration staining method to study the effects of insertion of microdialysis probes in rat dorsal hippocampus and neocortex. Nine animals were sacrificed 24 h, 3 days or 7 days after implantation of dialysis tubing. Although mild neuronal cell death and small petechial hemorrhages were seen in elose proximity to the implantation site, the striking finding was the presence of degenerating axons both adjacent to the implantation site and in remote sites such as the corpus callosum and contralateral hippocampus. The observed changes could alter brain function near or remote from the implantation site and should be considered in analysis of dialysis experiments. KW - Neurophysiologie KW - Neurobiologie KW - In-vivo dia lysis KW - Silver degeneration staining KW - Axonal degeneration KW - Rat hippocampus Y1 - 1990 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-47433 ER - TY - JOUR A1 - Talman, Arthur M. A1 - Prieto, Judith H. A1 - Marques, Sara A1 - Ubaida-Mohien, Ceereena A1 - Lawniczak, Mara A1 - Wass, Mark N. A1 - Xu, Tao A1 - Frank, Roland A1 - Ecker, Andrea A1 - Stanway, Rebecca S. A1 - Krishna, Sanjeev A1 - Sternberg, Michael J. E. A1 - Christophides, Georges K. A1 - Graham, David R. A1 - Dinglasan, Rhoel R. A1 - Yates, John R., III A1 - Sinden, Robert E. T1 - Proteomic analysis of the Plasmodium male gamete reveals the key role for glycolysis in flagellar motility JF - Malaria Journal N2 - Background: Gametogenesis and fertilization play crucial roles in malaria transmission. While male gametes are thought to be amongst the simplest eukaryotic cells and are proven targets of transmission blocking immunity, little is known about their molecular organization. For example, the pathway of energy metabolism that power motility, a feature that facilitates gamete encounter and fertilization, is unknown. Methods: Plasmodium berghei microgametes were purified and analysed by whole-cell proteomic analysis for the first time. Data are available via ProteomeXchange with identifier PXD001163. Results: 615 proteins were recovered, they included all male gamete proteins described thus far. Amongst them were the 11 enzymes of the glycolytic pathway. The hexose transporter was localized to the gamete plasma membrane and it was shown that microgamete motility can be suppressed effectively by inhibitors of this transporter and of the glycolytic pathway. Conclusions: This study describes the first whole-cell proteomic analysis of the malaria male gamete. It identifies glycolysis as the likely exclusive source of energy for flagellar beat, and provides new insights in original features of Plasmodium flagellar organization. KW - glycolysis KW - gamete KW - energy metabolism KW - tandem mass-spectra KW - YoelII-Nigeriensis KW - haemoproteus-columbae KW - chlamydomonas flagella KW - life cycle KW - microtubule motor KW - hexose transporter KW - membrane-protein topology KW - malaria parasite KW - subcellular localization KW - flagellum KW - plasmodium Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-115572 N1 - Additional files are available here: http://www.malariajournal.com/content/13/1/315/additional VL - 13 IS - 315 ER - TY - JOUR A1 - Gupta, Shishir K. A1 - Srivastava, Mugdha A1 - Osmanoglu, Özge A1 - Xu, Zhuofei A1 - Brakhage, Axel A. A1 - Dandekar, Thomas T1 - Aspergillus fumigatus versus genus Aspergillus: conservation, adaptive evolution and specific virulence genes JF - Microorganisms N2 - Aspergillus is an important fungal genus containing economically important species, as well as pathogenic species of animals and plants. Using eighteen fungal species of the genus Aspergillus, we conducted a comprehensive investigation of conserved genes and their evolution. This also allows us to investigate the selection pressure driving the adaptive evolution in the pathogenic species A. fumigatus. Among single-copy orthologs (SCOs) for A. fumigatus and the closely related species A. fischeri, we identified 122 versus 50 positively selected genes (PSGs), respectively. Moreover, twenty conserved genes of unknown function were established to be positively selected and thus important for adaption. A. fumigatus PSGs interacting with human host proteins show over-representation of adaptive, symbiosis-related, immunomodulatory and virulence-related pathways, such as the TGF-β pathway, insulin receptor signaling, IL1 pathway and interfering with phagosomal GTPase signaling. Additionally, among the virulence factor coding genes, secretory and membrane protein-coding genes in multi-copy gene families, 212 genes underwent positive selection and also suggest increased adaptation, such as fungal immune evasion mechanisms (aspf2), siderophore biosynthesis (sidD), fumarylalanine production (sidE), stress tolerance (atfA) and thermotolerance (sodA). These genes presumably contribute to host adaptation strategies. Genes for the biosynthesis of gliotoxin are shared among all the close relatives of A. fumigatus as an ancient defense mechanism. Positive selection plays a crucial role in the adaptive evolution of A. fumigatus. The genome-wide profile of PSGs provides valuable targets for further research on the mechanisms of immune evasion, antimycotic targeting and understanding fundamental virulence processes. KW - molecular evolution KW - phylogenetic analysis KW - adaptation KW - recombination KW - positive selection KW - human pathogenic fungi KW - genus Aspergillus KW - Aspergillus fumigatus Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-246318 SN - 2076-2607 VL - 9 IS - 10 ER -