@article{OttoHahlbrockEichetal.2016, author = {Otto, Christoph and Hahlbrock, Theresa and Eich, Kilian and Karaaslan, Ferdi and J{\"u}rgens, Constantin and Germer, Christoph-Thomas and Wiegering, Armin and K{\"a}mmerer, Ulrike}, title = {Antiproliferative and antimetabolic effects behind the anticancer property of fermented wheat germ extract}, series = {BMC Complementary and Alternative Medicine}, volume = {16}, journal = {BMC Complementary and Alternative Medicine}, number = {160}, doi = {10.1186/s12906-016-1138-5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-146013}, year = {2016}, abstract = {Background Fermented wheat germ extract (FWGE) sold under the trade name Avemar exhibits anticancer activity in vitro and in vivo. Its mechanisms of action are divided into antiproliferative and antimetabolic effects. Its influcence on cancer cell metabolism needs further investigation. One objective of this study, therefore, was to further elucidate the antimetabolic action of FWGE. The anticancer compound 2,6-dimethoxy-1,4-benzoquinone (DMBQ) is the major bioactive compound in FWGE and is probably responsible for its anticancer activity. The second objective of this study was to compare the antiproliferative properties in vitro of FWGE and the DMBQ compound. Methods The IC\(_{50}\) values of FWGE were determined for nine human cancer cell lines after 24 h of culture. The DMBQ compound was used at a concentration of 24 μmol/l, which is equal to the molar concentration of DMBQ in FWGE. Cell viability, cell cycle, cellular redox state, glucose consumption, lactic acid production, cellular ATP levels, and the NADH/NAD\(^+\) ratio were measured. Results The mean IC\(_{50}\) value of FWGE for the nine human cancer cell lines tested was 10 mg/ml. Both FWGE (10 mg/ml) and the DMBQ compound (24 μmol/l) induced massive cell damage within 24 h after starting treatment, with changes in the cellular redox state secondary to formation of intracellular reactive oxygen species. Unlike the DMBQ compound, which was only cytotoxic, FWGE exhibited cytostatic and growth delay effects in addition to cytotoxicity. Both cytostatic and growth delay effects were linked to impaired glucose utilization which influenced the cell cycle, cellular ATP levels, and the NADH/NAD\(^+\) ratio. The growth delay effect in response to FWGE treatment led to induction of autophagy. Conclusions FWGE and the DMBQ compound both induced oxidative stress-promoted cytotoxicity. In addition, FWGE exhibited cytostatic and growth delay effects associated with impaired glucose utilization which led to autophagy, a possible previously unknown mechanism behind the influence of FWGE on cancer cell metabolism.}, language = {en} } @phdthesis{Zimmermann2020, author = {Zimmermann, Henriette}, title = {Antigenic variation and stumpy development in \(Trypanosoma\) \(brucei\)}, doi = {10.25972/OPUS-14690}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-146902}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2020}, abstract = {The eukaryotic parasite Trypanosoma brucei has evolved sophisticated strategies to persist within its mammalian host. Trypanosomes evade the hosts' immune system by antigenic variation of their surface coat, consisting of variant surface glycoproteins (VSGs). Out of a repertoire of thousands of VSG genes, only one is expressed at any given time from one of the 15 telomeric expression sites (ES). The VSG is stochastically exchanged either by a transcriptional switch of the active ES (in situ switch) or by a recombinational exchange of the VSG within the active ES. However, for infections to persist, the parasite burden has to be limited. The slender (sl) bloodstream form secretes the stumpy induction factor (SIF), which accumulates with rising parasitemia. SIF induces the irreversible developmental transition from the proliferative sl to the cell cycle-arrested but fly-infective stumpy (st) stage once a concentration threshold is reached. Thus, antigenic variation and st development ensure persistent infections and transmissibility. A previous study in monomorphic cells indicated that the attenuation of the active ES could be relevant for the development of trypanosomes. The present thesis investigated this hypothesis using the inducible overexpression of an ectopic VSG in pleomorphic trypanosomes, which possess full developmental competence. These studies revealed a surprising phenotypic plasticity: while the endogenous VSG was always down-regulated upon induction, the ESactivity determined whether the VSG overexpressors arrested in growth or kept proliferating. Full ES-attenuation induced the differentiation of bona fide st parasites independent of the cell density and thus represents the sole natural SIF-independent differentiation trigger to date. A milder decrease of the ES-activity did not induce phenotypic changes, but appeared to prime the parasites for SIF-induced differentiation. These results demonstrate that antigenic variation and development are linked and indicated that the ES and the VSG are independently regulated. Therefore, I investigated in the second part of my thesis how ES-attenuation and VSG-silencing can be mediated. Integration of reporters with a functional or defective VSG 3'UTR into different genomic loci showed that the maintenance of the active state of the ES depends on a conserved motif within the VSG 3'UTR. In situ switching was only triggered when the telomere-proximal motif was partially deleted, suggesting that it serves as a DNA-binding motif for a telomere-associated protein. The VSG levels seem to be additionally regulated in trans based on the VSG 3'UTR independent of the genomic context, which was reinforced by the regulation of a constitutively expressed reporter with VSG 3' UTR upon ectopic VSG overexpression.}, subject = {Trypanosoma brucei}, language = {en} } @article{BonaScheerBautz1981, author = {Bona, Marion and Scheer, Ulrich and Bautz, Ekkehard K. F.}, title = {Antibodies to RNA polymerase II (B) inhibit transcription in lampbrush chromosomes after microinjection into living amphibian oocytes}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-33128}, year = {1981}, abstract = {Antibodies directed against RNA polymerase II (B) from Drosophila melanogaster were obtained from rabbit sera and, as monoclonal immunoglobulins, from mouse hybridomas and shown to cross-react with the amphibian enzyme protein. Localization by indirect immunofluorescence microscopy revealed the association of this enzyme with chromatin of interphase nuclei of amphibian cells and its absence in nucleoli. Purified immunoglobulins were microinjected in to nuclei ofliving vitellogenic oocytes of Ple1lrodeles waltlii and X enopus laevis and their effects on transcriptional processes were monitored by biochemical and light and electron microscopic stud ies. RNA polymerase II antibodies from rabbit sera caused a rapid and almost complete release of nascent transcripts from the chromatin axis of the loops of lampbrush chromosomes, followed by collapse of the loops and their retraction on the main chromosome axis. Monoclonal murine antibodies to the Iarge RNA polymerase II subunits also inhibited transcription in chromosome Ioops but appeared to inhibit initiation rather than elongation events. Activities of class land III RNA polymerases were not significantly affected by injection of antibodies to polymerase II, indicating immunological differences between the three RNA polymerases. The potential value of the in vitro test system described , as a very sensitive assay for detecting proteins involved in transcription in living cells, is discussed. 1}, language = {en} } @article{ColizziBeerCutietal.2021, author = {Colizzi, Francesca Sara and Beer, Katharina and Cuti, Paolo and Deppisch, Peter and Mart{\´i}nez Torres, David and Yoshii, Taishi and Helfrich-F{\"o}rster, Charlotte}, title = {Antibodies Against the Clock Proteins Period and Cryptochrome Reveal the Neuronal Organization of the Circadian Clock in the Pea Aphid}, series = {Frontiers in Physiology}, volume = {12}, journal = {Frontiers in Physiology}, issn = {1664-042X}, doi = {10.3389/fphys.2021.705048}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-242909}, year = {2021}, abstract = {Circadian clocks prepare the organism to cyclic environmental changes in light, temperature, or food availability. Here, we characterized the master clock in the brain of a strongly photoperiodic insect, the aphid Acyrthosiphon pisum, immunohistochemically with antibodies against A. pisum Period (PER), Drosophila melanogaster Cryptochrome (CRY1), and crab Pigment-Dispersing Hormone (PDH). The latter antibody detects all so far known PDHs and PDFs (Pigment-Dispersing Factors), which play a dominant role in the circadian system of many arthropods. We found that, under long days, PER and CRY are expressed in a rhythmic manner in three regions of the brain: the dorsal and lateral protocerebrum and the lamina. No staining was detected with anti-PDH, suggesting that aphids lack PDF. All the CRY1-positive cells co-expressed PER and showed daily PER/CRY1 oscillations of high amplitude, while the PER oscillations of the CRY1-negative PER neurons were of considerable lower amplitude. The CRY1 oscillations were highly synchronous in all neurons, suggesting that aphid CRY1, similarly to Drosophila CRY1, is light sensitive and its oscillations are synchronized by light-dark cycles. Nevertheless, in contrast to Drosophila CRY1, aphid CRY1 was not degraded by light, but steadily increased during the day and decreased during the night. PER was always located in the nuclei of the clock neurons, while CRY was predominantly cytoplasmic and revealed the projections of the PER/CRY1-positive neurons. We traced the PER/CRY1-positive neurons through the aphid protocerebrum discovering striking similarities with the circadian clock of D. melanogaster: The CRY1 fibers innervate the dorsal and lateral protocerebrum and putatively connect the different PER-positive neurons with each other. They also run toward the pars intercerebralis, which controls hormone release via the neurohemal organ, the corpora cardiaca. In contrast to Drosophila, the CRY1-positive fibers additionally travel directly toward the corpora cardiaca and the close-by endocrine gland, corpora allata. This suggests a direct link between the circadian clock and the photoperiodic control of hormone release that can be studied in the future.}, language = {en} } @article{BeierGaetschenbergerAzzamietal.2013, author = {Beier, Hildburg and G{\"a}tschenberger, Heike and Azzami, Klara and Tautz, J{\"u}rgen}, title = {Antibacterial Immune Competence of Honey Bees (Apis mellifera) Is Adapted to Different Life Stages and Environmental Risks}, series = {PLoS ONE}, journal = {PLoS ONE}, doi = {10.1371/journal.pone.0066415}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-96895}, year = {2013}, abstract = {The development of all honey bee castes proceeds through three different life stages all of which encounter microbial infections to a various extent. We have examined the immune strength of honey bees across all developmental stages with emphasis on the temporal expression of cellular and humoral immune responses upon artificial challenge with viable Escherichia coli bacteria. We employed a broad array of methods to investigate defence strategies of infected individuals: (a) fate of bacteria in the haemocoel; (b) nodule formation and (c) induction of antimicrobial peptides (AMPs). Newly emerged adult worker bees and drones were able to activate efficiently all examined immune reactions. The number of viable bacteria circulating in the haemocoel of infected bees declined rapidly by more than two orders of magnitude within the first 4-6 h post-injection (p.i.), coinciding with the occurrence of melanised nodules. Antimicrobial activity, on the other hand, became detectable only after the initial bacterial clearance. These two temporal patterns of defence reactions very likely represent the constitutive cellular and the induced humoral immune response. A unique feature of honey bees is that a fraction of worker bees survives the winter season in a cluster mostly engaged in thermoregulation. We show here that the overall immune strength of winter bees matches that of young summer bees although nodulation reactions are not initiated at all. As expected, high doses of injected viable E.coli bacteria caused no mortality in larvae or adults of each age. However, drone and worker pupae succumbed to challenge with E.coli even at low doses, accompanied by a premature darkening of the pupal body. In contrast to larvae and adults, we observed no fast clearance of viable bacteria and no induction of AMPs but a rapid proliferation of E.coli bacteria in the haemocoel of bee pupae ultimately leading to their death.}, language = {en} } @article{BecamWalterBurgertetal.2017, author = {Becam, J{\´e}r{\^o}me and Walter, Tim and Burgert, Anne and Schlegel, Jan and Sauer, Markus and Seibel, J{\"u}rgen and Schubert-Unkmeir, Alexandra}, title = {Antibacterial activity of ceramide and ceramide analogs against pathogenic Neisseria}, series = {Scientific Reports}, volume = {7}, journal = {Scientific Reports}, doi = {10.1038/s41598-017-18071-w}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-159367}, pages = {17627}, year = {2017}, abstract = {Certain fatty acids and sphingoid bases found at mucosal surfaces are known to have antibacterial activity and are thought to play a more direct role in innate immunity against bacterial infections. Herein, we analysed the antibacterial activity of sphingolipids, including the sphingoid base sphingosine as well as short-chain C\(_{6}\) and long-chain C\(_{16}\)-ceramides and azido-functionalized ceramide analogs against pathogenic Neisseriae. Determination of the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) demonstrated that short-chain ceramides and a ω-azido-functionalized C\(_{6}\)-ceramide were active against Neisseria meningitidis and N. gonorrhoeae, whereas they were inactive against Escherichia coli and Staphylococcus aureus. Kinetic assays showed that killing of N. meningitidis occurred within 2 h with ω-azido-C\(_{6}\)-ceramide at 1 X the MIC. Of note, at a bactericidal concentration, ω-azido-C\(_{6}\)-ceramide had no significant toxic effect on host cells. Moreover, lipid uptake and localization was studied by flow cytometry and confocal laser scanning microscopy (CLSM) and revealed a rapid uptake by bacteria within 5 min. CLSM and super-resolution fluorescence imaging by direct stochastic optical reconstruction microscopy demonstrated homogeneous distribution of ceramide analogs in the bacterial membrane. Taken together, these data demonstrate the potent bactericidal activity of sphingosine and synthetic short-chain ceramide analogs against pathogenic Neisseriae.}, language = {en} } @article{DopplerSchusterAppeltshauseretal.2019, author = {Doppler, Kathrin and Schuster, Yasmin and Appeltshauser, Luise and Biko, Lydia and Villmann, Carmen and Weishaupt, Andreas and Werner, Christian and Sommer, Claudia}, title = {Anti-CNTN1 IgG3 induces acute conduction block and motor deficits in a passive transfer rat model}, series = {Journal of Neuroinflammation}, volume = {16}, journal = {Journal of Neuroinflammation}, number = {73}, doi = {10.1186/s12974-019-1462-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-200476}, year = {2019}, abstract = {Background: Autoantibodies against the paranodal protein contactin-1 have recently been described in patients with severe acute-onset autoimmune neuropathies and mainly belong to the IgG4 subclass that does not activate complement. IgG3 anti-contactin-1 autoantibodies are rare, but have been detected during the acute onset of disease in some cases. There is evidence that anti-contactin-1 prevents adhesive interaction, and chronic exposure to anti-contactin-1 IgG4 leads to structural changes at the nodes accompanied by neuropathic symptoms. However, the pathomechanism of acute onset of disease and the pathogenic role of IgG3 anti-contactin-1 is largely unknown. Methods: In the present study, we aimed to model acute autoantibody exposure by intraneural injection of IgG of patients with anti-contacin-1 autoantibodies to Lewis rats. Patient IgG obtained during acute onset of disease (IgG3 predominant) and IgG from the chronic phase of disease (IgG4 predominant) were studied in comparison. Results: Conduction blocks were measured in rats injected with the "acute" IgG more often than after injection of "chronic" IgG (83.3\% versus 35\%) and proved to be reversible within a week after injection. Impaired nerve conduction was accompanied by motor deficits in rats after injection of the "acute" IgG but only minor structural changes of the nodes. Paranodal complement deposition was detected after injection of the "acute IgG". We did not detect any inflammatory infiltrates, arguing against an inflammatory cascade as cause of damage to the nerve. We also did not observe dispersion of paranodal proteins or sodium channels to the juxtaparanodes as seen in patients after chronic exposure to anti-contactin-1. Conclusions: Our data suggest that anti-contactin-1 IgG3 induces an acute conduction block that is most probably mediated by autoantibody binding and subsequent complement deposition and may account for acute onset of disease in these patients. This supports the notion of anti-contactin-1-associated neuropathy as a paranodopathy with the nodes of Ranvier as the site of pathogenesis.}, language = {en} } @article{WohlwendCravenWeigeltetal.2021, author = {Wohlwend, Michael R. and Craven, Dylan and Weigelt, Patrick and Seebens, Hanno and Winter, Marten and Kreft, Holger and Zurell, Damaris and Sarmento Cabral, Juliano and Essl, Franz and van Kleunen, Mark and Pergl, Jan and Pyšek, Petr and Knight, Tiffany M.}, title = {Anthropogenic and environmental drivers shape diversity of naturalized plants across the Pacific}, series = {Diversity and Distributions}, volume = {27}, journal = {Diversity and Distributions}, number = {6}, doi = {10.1111/ddi.13260}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-239925}, pages = {1120 -- 1133}, year = {2021}, abstract = {Aim The Pacific exhibits an exceptional number of naturalized plant species, but the drivers of this high diversity and the associated compositional patterns remain largely unknown. Here, we aim to (a) improve our understanding of introduction and establishment processes and (b) evaluate whether this information is sufficient to create scientific conservation tools, such as watchlists. Location Islands in the Pacific Ocean, excluding larger islands such as New Zealand, Japan, the Philippines and Indonesia. Methods We combined information from the most up-to-date data sources to quantify naturalized plant species richness and turnover across island groups and investigate the effects of anthropogenic, biogeographic and climate drivers on these patterns. In total, we found 2,672 naturalized plant species across 481 islands and 50 island groups, with a total of 11,074 records. Results Most naturalized species were restricted to few island groups, and most island groups have a low number of naturalized species. Island groups with few naturalized species were characterized by a set of widespread naturalized species. Several plant families that contributed many naturalized species globally also did so in the Pacific, particularly Fabaceae and Poaceae. However, many families were significantly over- or under-represented in the Pacific naturalized flora compared to other regions of the world. Naturalized species richness increased primarily with increased human activity and island altitude/area, whereas similarity between island groups in temperature along with richness differences was most important for beta diversity. Main conclusions The distribution and richness of naturalized species can be explained by a small set of drivers. The Pacific region contains many naturalized plant species also naturalized in other regions in the world, but our results highlight key differences such as a stronger role of anthropogenic drivers in shaping diversity patterns. Our results establish a basis for predicting and preventing future naturalizations in a threatened biodiversity hotspot.}, language = {en} } @article{StiebKelberWehneretal.2011, author = {Stieb, Sara Mae and Kelber, Christina and Wehner, R{\"u}diger and R{\"o}ssler, Wolfgang}, title = {Antennal-Lobe Organization in Desert Ants of the Genus Cataglyphis}, series = {Brain, Behavior and Evolution}, volume = {77}, journal = {Brain, Behavior and Evolution}, number = {3}, issn = {0006-8977}, doi = {10.1159/000326211}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-196815}, pages = {136-146}, year = {2011}, abstract = {Desert ants of the genus Cataglyphis possess remarkable visual navigation capabilities. Although Cataglyphis species lack a trail pheromone system, Cataglyphis fortis employs olfactory cues for detecting nest and food sites. To investigate potential adaptations in primary olfactory centers of the brain of C. fortis, we analyzed olfactory glomeruli (odor processing units) in their antennal lobes and compared them to glomeruli in different Cataglyphis species. Using confocal imaging and 3D reconstruction, we analyzed the number, size and spatial arrangement of olfactory glomeruli in C. fortis, C.albicans, C.bicolor, C.rubra, and C.noda. Workers of all Cataglyphis species have smaller numbers of glomeruli (198-249) compared to those previously found in olfactory-guided ants. Analyses in 2 species of Formica - a genus closely related to Cataglyphis - revealed substantially higher numbers of olfactory glomeruli (c. 370), which is likely to reflect the importance of olfaction in these wood ant species. Comparisons between Cataglyphis species revealed 2 special features in C. fortis. First, with c. 198 C. fortis has the lowest number of glomeruli compared to all other species. Second, a conspicuously enlarged glomerulus is located close to the antennal nerve entrance. Males of C. fortis possess a significantly smaller number of glomeruli (c. 150) compared to female workers and queens. A prominent male-specific macroglomerulus likely to be involved in sex pheromone communication occupies a position different from that of the enlarged glomerulus in females. The behavioral significance of the enlarged glomerulus in female workers remains elusive. The fact that C. fortis inhabits microhabitats (salt pans) that are avoided by all other Cataglyphis species suggests that extreme ecological conditions may not only have resulted in adaptations of visual capabilities, but also in specializations of the olfactory system.}, language = {en} } @article{KimAmoresKangetal.2019, author = {Kim, Bo-Mi and Amores, Angel and Kang, Seunghyun and Ahn, Do-Hwan and Kim, Jin-Hyoung and Kim, Il-Chan and Lee, Jun Hyuck and Lee, Sung Gu and Lee, Hyoungseok and Lee, Jungeun and Kim, Han-Woo and Desvignes, Thomas and Batzel, Peter and Sydes, Jason and Titus, Tom and Wilson, Catherine A. and Catchen, Julian M. and Warren, Wesley C. and Schartl, Manfred and Detrich, H. William III and Postlethwait, John H. and Park, Hyun}, title = {Antarctic blackfin icefish genome reveals adaptations to extreme environments}, series = {Nature Ecology \& Evolution}, volume = {3}, journal = {Nature Ecology \& Evolution}, doi = {10.1038/s41559-019-0812-7}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-325811}, pages = {469-478}, year = {2019}, abstract = {Icefishes (suborder Notothenioidei; family Channichthyidae) are the only vertebrates that lack functional haemoglobin genes and red blood cells. Here, we report a high-quality genome assembly and linkage map for the Antarctic blackfin icefish Chaenocephalus aceratus, highlighting evolved genomic features for its unique physiology. Phylogenomic analysis revealed that Antarctic fish of the teleost suborder Notothenioidei, including icefishes, diverged from the stickleback lineage about 77 million years ago and subsequently evolved cold-adapted phenotypes as the Southern Ocean cooled to sub-zero temperatures. Our results show that genes involved in protection from ice damage, including genes encoding antifreeze glycoprotein and zona pellucida proteins, are highly expanded in the icefish genome. Furthermore, genes that encode enzymes that help to control cellular redox state, including members of the sod3 and nqo1 gene families, are expanded, probably as evolutionary adaptations to the relatively high concentration of oxygen dissolved in cold Antarctic waters. In contrast, some crucial regulators of circadian homeostasis (cry and per genes) are absent from the icefish genome, suggesting compromised control of biological rhythms in the polar light environment. The availability of the icefish genome sequence will accelerate our understanding of adaptation to extreme Antarctic environments.}, language = {en} }