TY - JOUR A1 - Peters, Marcell K. A1 - Hemp, Andreas A1 - Appelhans, Tim A1 - Behler, Christina A1 - Classen, Alice A1 - Detsch, Florian A1 - Ensslin, Andreas A1 - Ferger, Stefan W. A1 - Frederiksen, Sara B. A1 - Gebert, Frederike A1 - Haas, Michael A1 - Helbig-Bonitz, Maria A1 - Hemp, Claudia A1 - Kindeketa, William J. A1 - Mwangomo, Ephraim A1 - Ngereza, Christine A1 - Otte, Insa A1 - Röder, Juliane A1 - Rutten, Gemma A1 - Costa, David Schellenberger A1 - Tardanico, Joseph A1 - Zancolli, Giulia A1 - Deckert, Jürgen A1 - Eardley, Connal D. A1 - Peters, Ralph S. A1 - Rödel, Mark-Oliver A1 - Schleuning, Matthias A1 - Ssymank, Axel A1 - Kakengi, Victor A1 - Zhang, Jie A1 - Böhning-Gaese, Katrin A1 - Brandl, Roland A1 - Kalko, Elisabeth K.V. A1 - Kleyer, Michael A1 - Nauss, Thomas A1 - Tschapka, Marco A1 - Fischer, Markus A1 - Steffan-Dewenter, Ingolf T1 - Predictors of elevational biodiversity gradients change from single taxa to the multi-taxa community level JF - Nature Communications N2 - The factors determining gradients of biodiversity are a fundamental yet unresolved topic in ecology. While diversity gradients have been analysed for numerous single taxa, progress towards general explanatory models has been hampered by limitations in the phylogenetic coverage of past studies. By parallel sampling of 25 major plant and animal taxa along a 3.7 km elevational gradient on Mt. Kilimanjaro, we quantify cross-taxon consensus in diversity gradients and evaluate predictors of diversity from single taxa to a multi-taxa community level. While single taxa show complex distribution patterns and respond to different environmental factors, scaling up diversity to the community level leads to an unambiguous support for temperature as the main predictor of species richness in both plants and animals. Our findings illuminate the influence of taxonomic coverage for models of diversity gradients and point to the importance of temperature for diversification and species coexistence in plant and animal communities. KW - community ecology KW - macroecology KW - tropical ecology KW - biodiversity Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-169374 VL - 7 ER - TY - JOUR A1 - Jarausch, Johannes A1 - Neuenroth, Lisa A1 - Andag, Reiner A1 - Leha, Andreas A1 - Fischer, Andreas A1 - Asif, Abdul R. A1 - Lenz, Christof A1 - Eidizadeh, Abass T1 - Influence of shear stress, inflammation and BRD4 inhibition on human endothelial cells: a holistic proteomic approach JF - Cells N2 - Atherosclerosis is an important risk factor in the development of cardiovascular diseases. In addition to increased plasma lipid concentrations, irregular/oscillatory shear stress and inflammatory processes trigger atherosclerosis. Inhibitors of the transcription modulatory bromo- and extra-terminal domain (BET) protein family (BETi) could offer a possible therapeutic approach due to their epigenetic mechanism and anti-inflammatory properties. In this study, the influence of laminar shear stress, inflammation and BETi treatment on human endothelial cells was investigated using global protein expression profiling by ion mobility separation-enhanced data independent acquisition mass spectrometry (IMS-DIA-MS). For this purpose, primary human umbilical cord derived vascular endothelial cells were treated with TNFα to mimic inflammation and exposed to laminar shear stress in the presence or absence of the BRD4 inhibitor JQ1. IMS-DIA-MS detected over 4037 proteins expressed in endothelial cells. Inflammation, shear stress and BETi led to pronounced changes in protein expression patterns with JQ1 having the greatest effect. To our knowledge, this is the first proteomics study on primary endothelial cells, which provides an extensive database for the effects of shear stress, inflammation and BETi on the endothelial proteome. KW - HUVEC KW - shear stress KW - endothelial KW - proteomic KW - BRD4 KW - JQ1 KW - DIA-MS KW - BET Inhibitor KW - atherosclerosis Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-289872 SN - 2073-4409 VL - 11 IS - 19 ER - TY - JOUR A1 - Tony, Hans-Peter A1 - Burmester, Gerd A1 - Schulze-Koops, Hendrik A1 - Grunke, Mathias A1 - Henes, Joerg A1 - Kötter, Ina A1 - Haas, Judith A1 - Unger, Leonore A1 - Lovric, Svjetlana A1 - Haubitz, Marion A1 - Fischer-Betz, Rebecca A1 - Chehab, Gamal A1 - Rubbert-Roth, Andrea A1 - Specker, Christof A1 - Weinerth, Jutta A1 - Holle, Julia A1 - Müller-Ladner, Ulf A1 - König, Ramona A1 - Fiehn, Christoph A1 - Burgwinkel, Philip A1 - Budde, Klemens A1 - Sörensen, Helmut A1 - Meurer, Michael A1 - Aringer, Martin A1 - Kieseier, Bernd A1 - Erfurt-Berge, Cornelia A1 - Sticherling, Michael A1 - Veelken, Roland A1 - Ziemann, Ulf A1 - Strutz, Frank A1 - von Wussow, Praxis A1 - Meier, Florian MP A1 - Hunzelmann, Nico A1 - Schmidt, Enno A1 - Bergner, Raoul A1 - Schwarting, Andreas A1 - Eming, Rüdiger A1 - Schwarz-Eywill, Michael A1 - Wassenberg, Siegfried A1 - Fleck, Martin A1 - Metzler, Claudia A1 - Zettl, Uwe A1 - Westphal, Jens A1 - Heitmann, Stefan A1 - Herzog, Anna L. A1 - Wiendl, Heinz A1 - Jakob, Waltraud A1 - Schmidt, Elvira A1 - Freivogel, Klaus A1 - Dörner, Thomas A1 - Hertl, Michael A1 - Stadler, Rudolf T1 - Safety and clinical outcomes of rituximab therapy in patients with different autoimmune diseases: experience from a national registry (GRAID) JF - Arthritis Research & Therapy N2 - Introduction: Evidence from a number of open-label, uncontrolled studies has suggested that rituximab may benefit patients with autoimmune diseases who are refractory to standard-of-care. The objective of this study was to evaluate the safety and clinical outcomes of rituximab in several standard-of-care-refractory autoimmune diseases (within rheumatology, nephrology, dermatology and neurology) other than rheumatoid arthritis or non-Hodgkin’s lymphoma in a real-life clinical setting. Methods: Patients who received rituximab having shown an inadequate response to standard-of-care had their safety and clinical outcomes data retrospectively analysed as part of the German Registry of Autoimmune Diseases. The main outcome measures were safety and clinical response, as judged at the discretion of the investigators. Results: A total of 370 patients (299 patient-years) with various autoimmune diseases (23.0% with systemic lupus erythematosus, 15.7% antineutrophil cytoplasmic antibody-associated granulomatous vasculitides, 15.1% multiple sclerosis and 10.0% pemphigus) from 42 centres received a mean dose of 2,440 mg of rituximab over a median (range) of 194 (180 to 1,407) days. The overall rate of serious infections was 5.3 per 100 patient-years during rituximab therapy. Opportunistic infections were infrequent across the whole study population, and mostly occurred in patients with systemic lupus erythematosus. There were 11 deaths (3.0% of patients) after rituximab treatment (mean 11.6 months after first infusion, range 0.8 to 31.3 months), with most of the deaths caused by infections. Overall (n = 293), 13.3% of patients showed no response, 45.1% showed a partial response and 41.6% showed a complete response. Responses were also reflected by reduced use of glucocorticoids and various immunosuppressives during rituximab therapy and follow-up compared with before rituximab. Rituximab generally had a positive effect on patient well-being (physician’s visual analogue scale; mean improvement from baseline of 12.1 mm) KW - GRAID Y1 - 2011 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-142856 VL - 13 IS - R75 ER - TY - RPRT A1 - Pfeilschifter, Rene A1 - Lauth, Hans-Joachim A1 - Fischer, Doris A1 - Rothfuß, Eberhard A1 - Schachner, Andreas A1 - Schmitz, Barbara A1 - Werthmann, Katja T1 - Local Self-Governance in the Context of Weak Statehood in Antiquity and the Modern Era. A Program for a Fresh Perspective N2 - The nucleus of statehood is situated at the local level: in the village, the neighborhood, the city district. This is where a community, beyond the level of the family, first develops collective rules that are intended to ensure its continued existence. But usually this is not the only level of governance at play. Above it, there are supralocal formations of power, varying in scope from regional networks to empires, which supplement the local orders or compete with them. The premise of this Research Unit is that local forms of self-governance are especially heterogeneous and prominent, wherever supralocal statehood exists in the mode of weak permeation. The central question of our approach is how local forms of self-governance work in this context. We will examine the relations to the state level as well as to other local groups as they develop over time; the scope and spatial contingency of forms of self-governance; their legitimization and the interdependency with the organization and collective identity of those groups which carry them out; finally, we will turn our attention to the significance of self-governance for the configuration of weak statehood. The empirical focus will be at the local level, which has so far been largely neglected in the research on governance beyond the state. In order to achieve this, we will work with case studies that are structured by categories and situated in geographical areas and time periods that lie outside of modern Europe with its particular development of statehood since the Late Middle Ages: in Antiquity, and in the Global South of the present. By incorporating these different time frames, we hope to contribute to overcoming the dichotomy between the modern and pre-modern era, which is often given canonical status. Our goal is to create a comparative analysis of different configurations of order as well as the development of a typology of patterns of local governance. The structure of the empirical comparison itself promises methodological insights, since it will entail recognizing, dealing with, and overcoming disciplinary limitations. Starting with the identification of typical patterns and processes, we hope to gain a better grasp of the mechanisms by which local configurations of order succeed, while at the same time advancing the theoretical debate. This will allow us to make an interdisciplinary contribution to the understanding of fundamental elements of statehood and local governance that are of central importance, especially in the context of weak statehood. The insights we hope to gain by adopting this historical perspective will contribute to understanding a present that is not based exclusively on its own, seemingly completely new preconditions, and will thus significantly sharpen the political analysis of various forms of governance. T2 - Lokale Selbstregelungen im Kontext schwacher Staatlichkeit in Antike und Moderne. Ein Forschungsprogramm für einen Perspektivwechsel T3 - LoSAM Working Papers - 1(eng) KW - Begrenzte Staatlichkeit KW - Vergleichende politische Wissenschaft KW - Altertum KW - Geschichte KW - Moderne KW - Global South KW - weak statehood KW - local self-governance KW - interdisciplinarity Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-207371 SN - 2698-2684 N1 - Die deutsche Fassung dieses Working Papers ist unter https://doi.org/10.25972/OPUS-19347 verfügbar. ET - English Edition ER - TY - JOUR A1 - Wagner, Toni U. A1 - Fischer, Andreas A1 - Thoma, Eva C. A1 - Schartl, Manfred T1 - CrossQuery : A Web Tool for Easy Associative Querying of Transcriptome Data N2 - Enormous amounts of data are being generated by modern methods such as transcriptome or exome sequencing and microarray profiling. Primary analyses such as quality control, normalization, statistics and mapping are highly complex and need to be performed by specialists. Thereafter, results are handed back to biomedical researchers, who are then confronted with complicated data lists. For rather simple tasks like data filtering, sorting and cross-association there is a need for new tools which can be used by non-specialists. Here, we describe CrossQuery, a web tool that enables straight forward, simple syntax queries to be executed on transcriptome sequencing and microarray datasets. We provide deepsequencing data sets of stem cell lines derived from the model fish Medaka and microarray data of human endothelial cells. In the example datasets provided, mRNA expression levels, gene, transcript and sample identification numbers, GO-terms and gene descriptions can be freely correlated, filtered and sorted. Queries can be saved for later reuse and results can be exported to standard formats that allow copy-and-paste to all widespread data visualization tools such as Microsoft Excel. CrossQuery enables researchers to quickly and freely work with transcriptome and microarray data sets requiring only minimal computer skills. Furthermore, CrossQuery allows growing association of multiple datasets as long as at least one common point of correlated information, such as transcript identification numbers or GO-terms, is shared between samples. For advanced users, the object-oriented plug-in and event-driven code design of both server-side and client-side scripts allow easy addition of new features, data sources and data types. KW - CrossQuery Y1 - 2011 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-76088 ER - TY - JOUR A1 - Röhrich, Christian Rene A1 - Ngwa, Che Julius A1 - Wiesner, Jochen A1 - Schmidtberg, Henrike A1 - Degenkolb, Thomas A1 - Kollewe, Christian A1 - Fischer, Rainer A1 - Pradel, Gabriele A1 - Vilcinskas, Andreas T1 - Harmonine, a defence compound from the harlequin ladybird, inhibits mycobacterial growth and demonstrates multi-stage antimalarial activity JF - Biology Letters N2 - The harlequin ladybird beetle Harmonia axyridis has been introduced in many countries as a biological control agent, but has become an invasive species threatening the biodiversity of native ladybirds. Its invasive success has been attributed to its vigorous resistance against diverse pathogens. This study demonstrates that harmonine ((17R,9Z)-1,17-diaminooctadec-9-ene), which is present in H. axyridis haemolymph, displays broad-spectrum antimicrobial activity that includes human pathogens. Antibacterial activity is most pronounced against fast-growing mycobacteria and Mycobacterium tuberculosis, and the growth of both chloroquine-sensitive and -resistant Plasmodium falciparum strains is inhibited. Harmonine displays gametocytocidal activity, and inhibits the exflagellation of microgametocytes and zygote formation. In an Anopheles stephensi mosquito feeding model, harmonine displays transmission-blocking activity. KW - insect immunity KW - antimicrobial activity KW - harmonine KW - harmonia axyridis Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-127079 VL - 8 ER - TY - JOUR A1 - Ngwa, Che Julius A1 - Scheuermayer, Matthias A1 - Mair, Gunnar Rudolf A1 - Kern, Selina A1 - Brügl, Thomas A1 - Wirth, Christine Clara A1 - Aminake, Makoah Nigel A1 - Wiesner, Jochen A1 - Fischer, Rainer A1 - Vilcinskas, Andreas A1 - Pradel, Gabriele T1 - Changes in the transcriptome of the malaria parasite Plasmodium falciparum during the initial phase of transmission from the human to the mosquito JF - BMC Genomics N2 - Background: The transmission of the malaria parasite Plasmodium falciparum from the human to the mosquito is mediated by dormant sexual precursor cells, the gametocytes, which become activated in the mosquito midgut. Because gametocytes are the only parasite stages able to establish an infection in the mosquito, they play a crucial role in spreading the tropical disease. The human-to-mosquito transmission triggers important molecular changes in the gametocytes, which initiate gametogenesis and prepare the parasite for life-cycle progression in the insect vector. Results: To better understand gene regulations during the initial phase of malaria parasite transmission, we focused on the transcriptome changes that occur within the first half hour of parasite development in the mosquito. Comparison of mRNA levels of P. falciparum gametocytes before and 30 min following activation using suppression subtractive hybridization (SSH) identified 126 genes, which changed in expression during gametogenesis. Among these, 17.5% had putative functions in signaling, 14.3% were assigned to cell cycle and gene expression, 8.7% were linked to the cytoskeleton or inner membrane complex, 7.9% were involved in proteostasis and 6.4% in metabolism, 12.7% were cell surface-associated proteins, 11.9% were assigned to other functions, and 20.6% represented genes of unknown function. For 40% of the identified genes there has as yet not been any protein evidence. For a subset of 27 genes, transcript changes during gametogenesis were studied in detail by real-time RT-PCR. Of these, 22 genes were expressed in gametocytes, and for 15 genes transcript expression in gametocytes was increased compared to asexual blood stage parasites. Transcript levels of seven genes were particularly high in activated gametocytes, pointing at functions downstream of gametocyte transmission to the mosquito. For selected genes, a regulated expression during gametogenesis was confirmed on the protein level, using quantitative confocal microscopy. Conclusions: The obtained transcriptome data demonstrate the regulations of gene expression immediately following malaria parasite transmission to the mosquito. Our findings support the identification of proteins important for sexual reproduction and further development of the mosquito midgut stages and provide insights into the genetic basis of the rapid adaption of Plasmodium to the insect vector. KW - parasitophorous vacuole KW - sexual development KW - gametocyte KW - transcriptome KW - signal peptide peptidase KW - host cell interface KW - alpha-tubulin-II KW - life-cycle KW - protein kinases KW - in-vitro KW - erythroyte invation KW - blocking antibodies KW - malaria KW - plasmodium falciparum KW - gametogenesis KW - mosquito KW - transmission Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-121905 SN - 1471-2164 VL - 14 IS - 256 ER - TY - JOUR A1 - Feller, Tatjana A1 - Thom, Pascal A1 - Koch, Natalie A1 - Spiegel, Holger A1 - Addai-Mensah, Otchere A1 - Fischer, Rainer A1 - Reimann, Andreas A1 - Pradel, Gabriele A1 - Fendel, Rolf A1 - Schillberg, Stefan A1 - Scheuermayer, Matthias A1 - Schinkel, Helga T1 - Plant-Based Production of Recombinant Plasmodium Surface Protein Pf38 and Evaluation of its Potential as a Vaccine Candidate JF - PLOS ONE N2 - Pf38 is a surface protein of the malarial parasite Plasmodium falciparum. In this study, we produced and purified recombinant Pf38 and a fusion protein composed of red fluorescent protein and Pf38 (RFP-Pf38) using a transient expression system in the plant Nicotiana benthamiana. To our knowledge, this is the first description of the production of recombinant Pf38. To verify the quality of the recombinant Pf38, plasma from semi-immune African donors was used to confirm specific binding to Pf38. ELISA measurements revealed that immune responses to Pf38 in this African subset were comparable to reactivities to AMA-1 and \(MSP1_{19}\). Pf38 and RFP-Pf38 were successfully used to immunise mice, although titres from these mice were low (on average 1:11.000 and 1:39.000, respectively). In immune fluorescence assays, the purified IgG fraction from the sera of immunised mice recognised Pf38 on the surface of schizonts, gametocytes, macrogametes and zygotes, but not sporozoites. Growth inhibition assays using \(\alpha Pf38\) antibodies demonstrated strong inhibition \((\geq 60 \% ) \) of the growth of blood-stage P. falciparum. The development of zygotes was also effectively inhibited by \(\alpha Pf38\) antibodies, as determined by the zygote development assay. Collectively, these results suggest that Pf38 is an interesting candidate for the development of a malaria vaccine. KW - malaria vaccine KW - balancing selection KW - N-glycans KW - falciparum KW - expression KW - antibodies KW - identification KW - transmission KW - tobacco KW - antigen Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-128221 SN - 1932-6203 VL - 8 IS - 11 ER - TY - JOUR A1 - von Bohl, Andreas A1 - Kuehn, Andrea A1 - Simon, Nina A1 - Nkwouano Ngongang, Vanesa A1 - Spehr, Marc A1 - Baumeister, Stefan A1 - Przyborski, Jude M. A1 - Fischer, Rainer A1 - Pradel, Gabriele T1 - A WD40-repeat protein unique to malaria parasites associates with adhesion protein complexes and is crucial for blood stage progeny JF - Malaria Journal N2 - Background During development in human erythrocytes, Plasmodium falciparum parasites display a remarkable number of adhesive proteins on their plasma membrane. In the invasive merozoites, these include members of the PfMSP1 and PfAMA1/RON complexes, which facilitate contact between merozoites and red blood cells. In gametocytes, sexual precursor cells mediating parasite transmission to the mosquito vector, plasma membrane-associated proteins primarily belong to the PfCCp and 6-cys families with roles in fertilization. This study describes a newly identified WD40-repeat protein unique to Plasmodium species that associates with adhesion protein complexes of both merozoites and gametocytes. Methods The WD40-repeat protein-like protein PfWLP1 was identified via co-immunoprecipitation assays followed by mass spectrometry and characterized using biochemical and immunohistochemistry methods. Reverse genetics were employed for functional analysis. Results PfWLP1 is expressed both in schizonts and gametocytes. In mature schizonts, the protein localizes underneath the merozoite micronemes and interacts with PfAMA1, while in gametocytes PfWLP1 primarily accumulates underneath the plasma membrane and associates with PfCCp1 and Pfs230. Reverse genetics failed to disrupt the pfwlp1 gene, while haemagglutinin-tagging was feasible, suggesting a crucial function for PfWLP1 during blood stage replication. Conclusions This is the first report on a plasmodial WD40-repeat protein associating with cell adhesion proteins. Since WD40 domains are known to mediate protein–protein contact by serving as a rigid scaffold for protein interactions, the presented data suggest that PfWLP1 supports the stability of adhesion protein complexes of the plasmodial blood stages. KW - PfCCp protein KW - Pfs230 KW - PfAMA1 KW - WD40 KW - gametocyte KW - microneme KW - merozoite KW - plasmodium falciparum KW - malaria Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-139728 VL - 14 IS - 435 ER - TY - JOUR A1 - Beiss, Veronique A1 - Spiegel, Holger A1 - Boes, Alexander A1 - Scheuermayer, Matthias A1 - Reimann, Andreas A1 - Schillberg, Stefan A1 - Fischer, Rainer T1 - Plant expression and characterization of the transmission-blocking vaccine candidate PfGAP50 JF - BMC Biotechnology N2 - Background: Despite the limited success after decades of intensive research and development efforts, vaccination still represents the most promising strategy to significantly reduce the disease burden in malaria endemic regions. Besides the ultimate goal of inducing sterile protection in vaccinated individuals, the prevention of transmission by so-called transmission blocking vaccines (TBVs) is being regarded as an important feature of an efficient malaria eradication strategy. Recently, Plasmodium falciparum GAP50 (PfGAP50), a 44.6 kDa transmembrane protein that forms an essential part of the invasion machinery (glideosome) multi-protein complex, has been proposed as novel potential transmission-blocking candidate. Plant-based expression systems combine the advantages of eukaryotic expression with a up-scaling potential and a good product safety profile suitable for vaccine production. In this study we investigated the feasibility to use the transient plant expression to produce PfGAP50 suitable for the induction of parasite specific inhibitory antibodies. Results: We performed the transient expression of recombinant PfGAP50 in Nicotiana benthamiana leaves using endoplasmatic reticulum (ER) and plastid targeting. After IMAC-purification the protein yield and integrity was investigated by SDS-PAGE and Western Blot. Rabbit immune IgG derived by the immunization with the plastidtargeted variant of PfGAP50 was analyzed by immune fluorescence assay (IFA) and zygote inhibition assay (ZIA). PfGAP50 could be produced in both subcellular compartments at different yields IMAC (Immobilized Metal Affinity Chromatography) purification from extract yielded up to 4.1 mu g/g recombinant protein per fresh leaf material for ER-retarded and 16.2 mu g/g recombinant protein per fresh leave material for plasmid targeted PfGAP50, respectively. IgG from rabbit sera generated by immunization with the recombinant protein specifically recognized different parasite stages in immunofluorescence assay. Furthermore up to 55 % inhibition in an in vitro zygote inhibition assay could be achieved using PfGAP50-specific rabbit immune IgG. Conclusions: The results of this study demonstrate that the plant-produced PfGAP50 is functional regarding the presentation of inhibitory epitopes and could be considered as component of a transmission-blocking malaria vaccine formulation. KW - PFS25 KW - plastid targeting KW - plant-made vaccines KW - agroinfiltration KW - gametes KW - sexual stage KW - plasmodium falciparum KW - membrane KW - antibodies KW - immunization KW - RTS,S/AS01 malaria vaccine KW - recombinant proteins KW - cost-effectiveness KW - purification Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-137327 VL - 15 IS - 108 ER -