TY - JOUR A1 - Tiegs, Scott D. A1 - Costello, David M. A1 - Isken, Mark W. A1 - Woodward, Guy A1 - McIntyre, Peter B. A1 - Gessner, Mark O. A1 - Chauvet, Eric A1 - Griffiths, Natalie A. A1 - Flecker, Alex S. A1 - Acuna, Vicenc A1 - Albarino, Ricardo A1 - Allen, Daniel C. A1 - Alonso, Cecilia A1 - Andino, Patricio A1 - Arango, Clay A1 - Aroviita, Jukka A1 - Barbosa, Marcus V. M. A1 - Barmuta, Leon A. A1 - Baxter, Colden V. A1 - Bell, Thomas D. C. A1 - Bellinger, Brent A1 - Boyero, Luz A1 - Brown, Lee E. A1 - Bruder, Andreas A1 - Bruesewitz, Denise A. A1 - Burdon, Francis J. A1 - Callisto, Marcos A1 - Canhoto, Cristina A1 - Capps, Krista A. A1 - Castillo, Maria M. A1 - Clapcott, Joanne A1 - Colas, Fanny A1 - Colon-Gaud, Checo A1 - Cornut, Julien A1 - Crespo-Perez, Veronica A1 - Cross, Wyatt F. A1 - Culp, Joseph M. A1 - Danger, Michael A1 - Dangles, Olivier A1 - de Eyto, Elvira A1 - Derry, Alison M. A1 - Diaz Villanueva, Veronica A1 - Douglas, Michael M. A1 - Elosegi, Arturo A1 - Encalada, Andrea C. A1 - Entrekin, Sally A1 - Espinosa, Rodrigo A1 - Ethaiya, Diana A1 - Ferreira, Veronica A1 - Ferriol, Carmen A1 - Flanagan, Kyla M. A1 - Fleituch, Tadeusz A1 - Shah, Jennifer J. Follstad A1 - Frainer, Andre A1 - Friberg, Nikolai A1 - Frost, Paul C. A1 - Garcia, Erica A. A1 - Lago, Liliana Garcia A1 - Garcia Soto, Pavel Ernesto A1 - Ghate, Sudeep A1 - Giling, Darren P. A1 - Gilmer, Alan A1 - Goncalves, Jose Francisco A1 - Gonzales, Rosario Karina A1 - Graca, Manuel A. S. A1 - Grace, Mike A1 - Grossart, Hans-Peter A1 - Guerold, Francois A1 - Gulis, Vlad A1 - Hepp, Luiz U. A1 - Higgins, Scott A1 - Hishi, Takuo A1 - Huddart, Joseph A1 - Hudson, John A1 - Imberger, Samantha A1 - Iniguez-Armijos, Carlos A1 - Iwata, Tomoya A1 - Janetski, David J. A1 - Jennings, Eleanor A1 - Kirkwood, Andrea E. A1 - Koning, Aaron A. A1 - Kosten, Sarian A1 - Kuehn, Kevin A. A1 - Laudon, Hjalmar A1 - Leavitt, Peter R. A1 - Lemes da Silva, Aurea L. A1 - Leroux, Shawn J. A1 - Leroy, Carri J. A1 - Lisi, Peter J. A1 - MacKenzie, Richard A1 - Marcarelli, Amy M. A1 - Masese, Frank O. A1 - Mckie, Brendan G. A1 - Oliveira Medeiros, Adriana A1 - Meissner, Kristian A1 - Milisa, Marko A1 - Mishra, Shailendra A1 - Miyake, Yo A1 - Moerke, Ashley A1 - Mombrikotb, Shorok A1 - Mooney, Rob A1 - Moulton, Tim A1 - Muotka, Timo A1 - Negishi, Junjiro N. A1 - Neres-Lima, Vinicius A1 - Nieminen, Mika L. A1 - Nimptsch, Jorge A1 - Ondruch, Jakub A1 - Paavola, Riku A1 - Pardo, Isabel A1 - Patrick, Christopher J. A1 - Peeters, Edwin T. H. M. A1 - Pozo, Jesus A1 - Pringle, Catherine A1 - Prussian, Aaron A1 - Quenta, Estefania A1 - Quesada, Antonio A1 - Reid, Brian A1 - Richardson, John S. A1 - Rigosi, Anna A1 - Rincon, Jose A1 - Risnoveanu, Geta A1 - Robinson, Christopher T. A1 - Rodriguez-Gallego, Lorena A1 - Royer, Todd V. A1 - Rusak, James A. A1 - Santamans, Anna C. A1 - Selmeczy, Geza B. A1 - Simiyu, Gelas A1 - Skuja, Agnija A1 - Smykla, Jerzy A1 - Sridhar, Kandikere R. A1 - Sponseller, Ryan A1 - Stoler, Aaron A1 - Swan, Christopher M. A1 - Szlag, David A1 - Teixeira-de Mello, Franco A1 - Tonkin, Jonathan D. A1 - Uusheimo, Sari A1 - Veach, Allison M. A1 - Vilbaste, Sirje A1 - Vought, Lena B. M. A1 - Wang, Chiao-Ping A1 - Webster, Jackson R. A1 - Wilson, Paul B. A1 - Woelfl, Stefan A1 - Xenopoulos, Marguerite A. A1 - Yates, Adam G. A1 - Yoshimura, Chihiro A1 - Yule, Catherine M. A1 - Zhang, Yixin X. A1 - Zwart, Jacob A. T1 - Global patterns and drivers of ecosystem functioning in rivers and riparian zones JF - Science Advances N2 - River ecosystems receive and process vast quantities of terrestrial organic carbon, the fate of which depends strongly on microbial activity. Variation in and controls of processing rates, however, are poorly characterized at the global scale. In response, we used a peer-sourced research network and a highly standardized carbon processing assay to conduct a global-scale field experiment in greater than 1000 river and riparian sites. We found that Earth’s biomes have distinct carbon processing signatures. Slow processing is evident across latitudes, whereas rapid rates are restricted to lower latitudes. Both the mean rate and variability decline with latitude, suggesting temperature constraints toward the poles and greater roles for other environmental drivers (e.g., nutrient loading) toward the equator. These results and data set the stage for unprecedented “next-generation biomonitoring” by establishing baselines to help quantify environmental impacts to the functioning of ecosystems at a global scale. Y1 - 2019 U6 - https://doi.org/10.1126/sciadv.aav0486 SN - 2375-2548 VL - 5 IS - 1 PB - American Assoc. for the Advancement of Science CY - Washington ER - TY - JOUR A1 - von Loeffelholz, Christian A1 - Lieske, Stefanie A1 - Neuschaefer-Rube, Frank A1 - Willmes, Diana M. A1 - Raschzok, Nathanael A1 - Sauer, Igor M. A1 - König, Jörg A1 - Fromm, Martin F. A1 - Horn, Paul A1 - Chatzigeorgiou, Antonios A1 - Pathe-Neuschaefer-Rube, Andrea A1 - Jordan, Jens A1 - Pfeiffer, Andreas F. H. A1 - Mingrone, Geltrude A1 - Bornstein, Stefan R. A1 - Stroehle, Peter A1 - Harms, Christoph A1 - Wunderlich, F. Thomas A1 - Helfand, Stephen L. A1 - Bernier, Michel A1 - de Cabo, Rafael A1 - Shulman, Gerald I. A1 - Chavakis, Triantafyllos A1 - Püschel, Gerhard Paul A1 - Birkenfeld, Andreas L. T1 - The human longevity gene homolog INDY and interleukin-6 interact in hepatic lipid metabolism BT - official journal of the American Association for the Study of Liver Diseases JF - Hepatology N2 - Reduced expression of the Indy ("I am Not Dead, Yet") gene in lower organisms promotes longevity in a manner akin to caloric restriction. Deletion of the mammalian homolog of Indy (mIndy, Slc13a5) encoding for a plasma membrane-associated citrate transporter expressed highly in the liver, protects mice from high-fat diet-induced and aging-induced obesity and hepatic fat accumulation through a mechanism resembling caloric restriction. We studied a possible role of mIndy in human hepatic fat metabolism. In obese, insulin-resistant patients with nonalcoholic fatty liver disease, hepatic mIndy expression was increased and mIndy expression was also independently associated with hepatic steatosis. In nonhuman primates, a 2-year high-fat, high-sucrose diet increased hepatic mIndy expression. Liver microarray analysis showed that high mIndy expression was associated with pathways involved in hepatic lipid metabolism and immunological processes. Interleukin-6 (IL-6) was identified as a regulator of mIndy by binding to its cognate receptor. Studies in human primary hepatocytes confirmed that IL-6 markedly induced mIndy transcription through the IL-6 receptor and activation of the transcription factor signal transducer and activator of transcription 3, and a putative start site of the human mIndy promoter was determined. Activation of the IL-6-signal transducer and activator of transcription 3 pathway stimulated mIndy expression, enhanced cytoplasmic citrate influx, and augmented hepatic lipogenesis in vivo. In contrast, deletion of mIndy completely prevented the stimulating effect of IL-6 on citrate uptake and reduced hepatic lipogenesis. These data show that mIndy is increased in liver of obese humans and nonhuman primates with NALFD. Moreover, our data identify mIndy as a target gene of IL-6 and determine novel functions of IL-6 through mINDY. Conclusion: Targeting human mINDY may have therapeutic potential in obese patients with nonalcoholic fatty liver disease. German Clinical Trials Register: DRKS00005450. Y1 - 2017 U6 - https://doi.org/10.1002/hep.29089 SN - 0270-9139 SN - 1527-3350 VL - 66 IS - 2 SP - 616 EP - 630 PB - Wiley CY - Hoboken ER - TY - JOUR A1 - Frodl, Thomas A1 - Janowitz, Deborah A1 - Schmaal, Lianne A1 - Tozzi, Leonardo A1 - Dobrowolny, Henrik A1 - Stein, Dan J. A1 - Veltman, Dick J. A1 - Wittfeld, Katharina A1 - van Erp, Theo G. M. A1 - Jahanshad, Neda A1 - Block, Andrea A1 - Hegenscheid, Katrin A1 - Voelzke, Henry A1 - Lagopoulos, Jim A1 - Hatton, Sean N. A1 - Hickie, Ian B. A1 - Frey, Eva Maria A1 - Carballedo, Angela A1 - Brooks, Samantha J. A1 - Vuletic, Daniella A1 - Uhlmann, Anne A1 - Veer, Ilya M. A1 - Walter, Henrik A1 - Schnell, Knut A1 - Grotegerd, Dominik A1 - Arolt, Volker A1 - Kugel, Harald A1 - Schramm, Elisabeth A1 - Konrad, Carsten A1 - Zurowski, Bartosz A1 - Baune, Bernhard T. A1 - van der Wee, Nic J. A. A1 - van Tol, Marie-Jose A1 - Penninx, Brenda W. J. H. A1 - Thompson, Paul M. A1 - Hibar, Derrek P. A1 - Dannlowski, Udo A1 - Grabe, Hans J. T1 - Childhood adversity impacts on brain subcortical structures relevant to depression JF - Journal of psychiatric research N2 - Childhood adversity plays an important role for development of major depressive disorder (MDD). There are differences in subcortical brain structures between patients with MDD and healthy controls, but the specific impact of childhood adversity on such structures in MDD remains unclear. Thus, aim of the present study was to investigate whether childhood adversity is associated with subcortical volumes and how it interacts with a diagnosis of MDD and sex. Within the ENIGMA-MDD network, nine university partner sites, which assessed childhood adversity and magnetic resonance imaging in patients with MDD and controls, took part in the current joint mega-analysis. In this largest effort world-wide to identify subcortical brain structure differences related to childhood adversity, 3036 participants were analyzed for subcortical brain volumes using FreeSurfer. A significant interaction was evident between childhood adversity, MDD diagnosis, sex, and region. Increased exposure to childhood adversity was associated with smaller caudate volumes in females independent of MDD. All subcategories of childhood adversity were negatively associated with caudate volumes in females - in particular emotional neglect and physical neglect (independently from age, ICV, imaging site and MDD diagnosis). There was no interaction effect between childhood adversity and MDD diagnosis on subcortical brain volumes. Childhood adversity is one of the contributors to brain structural abnormalities. It is associated with subcortical brain abnormalities that are relevant to psychiatric disorders such as depression. (C) 2016 Published by Elsevier Ltd. KW - Depression KW - Childhood adversity KW - MRI KW - Caudate KW - Hippocampus KW - ENIGMA Y1 - 2016 U6 - https://doi.org/10.1016/j.jpsychires.2016.11.010 SN - 0022-3956 SN - 1879-1379 VL - 86 SP - 58 EP - 65 PB - Elsevier CY - Oxford ER - TY - JOUR A1 - Creighton, Andrea L. A1 - Parsekian, Andrew D. A1 - Angelopoulos, Michael A1 - Jones, Benjamin M. A1 - Bondurant, A. A1 - Engram, M. A1 - Lenz, Josefine A1 - Overduin, Pier Paul A1 - Grosse, Guido A1 - Babcock, E. A1 - Arp, Christopher D. T1 - Transient Electromagnetic Surveys for the Determination of Talik Depth and Geometry Beneath Thermokarst Lakes JF - Journal of geophysical research : Solid earth N2 - Thermokarst lakes are prevalent in Arctic coastal lowland regions and sublake permafrost degradation and talik development contributes to greenhouse gas emissions by tapping the large permafrost carbon pool. Whereas lateral thermokarst lake expansion is readily apparent through remote sensing and shoreline measurements, sublake thawed sediment conditions and talik growth are difficult to measure. Here we combine transient electromagnetic surveys with thermal modeling, backed up by measured permafrost properties and radiocarbon ages, to reveal closed-talik geometry associated with a thermokarst lake in continuous permafrost. To improve access to talik geometry data, we conducted surveys along three transient electromagnetic transects perpendicular to lakeshores with different decadal-scale expansion rates of 0.16, 0.38, and 0.58m/year. We modeled thermal development of the talik using boundary conditions based on field data from the lake, surrounding permafrost and a borehole, independent of the transient electromagnetics. A talik depth of 91m was determined from analysis of the transient electromagnetic surveys. Using a lake initiation age of 1400years before present and available subsurface properties the results from thermal modeling of the lake center arrived at a best estimate talk depth of 80m, which is on the same order of magnitude as the results from the transient electromagnetic survey. Our approach has provided a noninvasive estimate of talik geometry suitable for comparable settings throughout circum-Arctic coastal lowland regions. KW - geophysics KW - permafrost KW - thermokarst KW - electromagnetic KW - lake Y1 - 2018 U6 - https://doi.org/10.1029/2018JB016121 SN - 2169-9313 SN - 2169-9356 VL - 123 IS - 11 SP - 9310 EP - 9323 PB - American Geophysical Union CY - Washington ER - TY - GEN A1 - Pathe-Neuschäfer-Rube, Andrea A1 - Neuschäfer-Rube, Frank A1 - Haas, Gerald A1 - Langoth-Fehringer, Nina A1 - Püschel, Gerhard Paul T1 - Cell-Based Reporter Release Assay to Determine the Potency of Proteolytic Bacterial Neurotoxins T2 - Toxins N2 - Despite the implementation of cell-based replacement methods, the mouse lethality assay is still frequently used to determine the activity of botulinum toxin (BoNT) for medical use. One explanation is that due to the use of neoepitope-specific antibodies to detect the cleaved BoNT substrate, the currently devised assays can detect only one specific serotype of the toxin. Recently, we developed a cell-based functional assay, in which BoNT activity is determined by inhibiting the release of a reporter enzyme that is liberated concomitantly with the neurotransmitter from neurosecretory vesicles. In theory, this assay should be suitable to detect the activity of any BoNT serotype. Consistent with this assumption, the current study shows that the stimulus-dependent release of a luciferase from a differentiated human neuroblastoma-based reporter cell line (SIMA-hPOMC1-26-GLuc cells) was inhibited by BoNT-A and-C. Furthermore, this was also inhibited by BoNT-B and tetanus toxin to a lesser extent and at higher concentrations. In order to provide support for the suitability of this technique in practical applications, a dose–response curve obtained with a pharmaceutical preparation of BoNT-A closely mirrored the activity determined in the mouse lethality assay. In summary, the newly established cell-based assay may represent a versatile and specific alternative to the mouse lethality assay and other currently established cell-based assays. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 473 KW - botulinum toxin KW - BoNT KW - tetanus toxin KW - RRR KW - replacement Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-418141 ER - TY - JOUR A1 - Henkel, Janin A1 - Neuschaefer-Rube, Frank A1 - Pathe-Neuschaefer-Rube, Andrea A1 - Püschel, Gerhard Paul T1 - Aggravation by prostaglandin e-2 of interleukin-6-dependent insulin resistance in hepatocytes N2 - Hepatic insulin resistance is a major contributor to fasting hyperglycemia in patients with metabolic syndrome and type 2 diabetes. Circumstantial evidence suggests that cyclooxygenase products in addition to cytokines might contribute to insulin resistance. However, direct evidence for a role of prostaglandins in the development of hepatic insulin resistance is lacking. Therefore, the impact of prostaglandin E-2 (PGE(2)) alone and in combination with interleukin-6 (IL-6) on insulin signaling was studied in primary hepatocyte cultures. Rat hepatocytes were incubated with IL-6 and/or PGE(2) and subsequently with insulin. Glycogen synthesis was monitored by radiochemical analysis; the activation state of proteins of the insulin receptor signal chain was analyzed by western blot with phosphospecific antibodies. In hepatocytes, insulin-stimulated glycogen synthesis and insulin-dependent phosphorylation of Akt-kinase were attenuated synergistically by prior incubation with IL-6 and/or PGE(2) while insulin receptor autophosphorylation was barely affected. IL-6 but not PGE(2) induced suppressors of cytokine signaling (SOCS3). PGE(2) but not IL-6 activated extracellular signal-regulated kinase 1/2 (ERK1/2) persistently. Inhibition of ERK1/2 activation by PD98059 abolished the PGE(2)-dependent but not the IL-6-dependent attenuation of insulin signaling. In HepG2 cells expressing a recombinant EP3-receptor, PGE(2) pre-incubation activated ERK1/2, caused a serine phosphorylation of insulin receptor substrate 1 (IRS1), and reduced the insulin-dependent Akt-phosphorylation. Conclusion: PGE(2) might contribute to hepatic insulin resistance via an EP3-receptor-dependent ERK1/2 activation resulting in a serine phosphorylation of insulin receptor substrate, thereby preventing an insulin-dependent activation of Akt and glycogen synthesis. Since different molecular mechanisms appear to be employed, PGE(2) may synergize with IL-6, which interrupted the insulin receptor signal chain, principally by an induction of SOCS, namely SOCS3. Y1 - 2009 UR - http://onlinelibrary.wiley.com/journal/10.1002/%28ISSN%291527-3350 U6 - https://doi.org/10.1002/Hep.23064 SN - 0270-9139 ER - TY - JOUR A1 - Pathe-Neuschaefer-Rube, Andrea A1 - Neuschaefer-Rube, Frank A1 - Genz, Lara A1 - Püschel, Gerhard Paul T1 - Botulinum Neurotoxin Dose-Dependently Inhibits Release of Neurosecretory Vesicle-Targeted Luciferase from Neuronal Cells JF - Alternatives to animal experimentation : ALTEX ; a journal for new paths in biomedical science N2 - Botulinum toxin is a bacterial toxin that inhibits neurotransmitter release from neurons and thereby causes a flaccid paralysis. It is used as drug to treat a number of serious ailments and, more frequently, for aesthetic medical interventions. Botulinum toxin for pharmacological applications is isolated from bacterial cultures. Due to partial denaturation of the protein, the specific activity of these preparations shows large variations. Because of its extreme potential toxicity, pharmacological preparations must be carefully tested for their activity. For the current gold standard, the mouse lethality assay, several hundred thousand mice are killed per year. Alternative methods have been developed that suffer from one or more of the following deficits: In vitro enzyme assays test only the activity of the catalytic subunit of the toxin. Enzymatic and cell based immunological assays are specific for just one of the different serotypes. The current study takes a completely different approach that overcomes these limitations: Neuronal cell lines were stably transfected with plasmids coding for luciferases of different species, which were N-terminally tagged with leader sequences that redirect the luciferase into neuro-secretory vesicles. From these vesicles, luciferases were released upon depolarization of the cells. The depolarization-dependent release was efficiently inhibited by botulinum toxin in a concentration range (1 to 100 pM) that is used in pharmacological preparations. The new assay might thus be an alternative to the mouse lethality assay and the immunological assays already in use. KW - Botulinum toxin KW - cell-based assay KW - mouse lethality assay Y1 - 2015 SN - 1868-596X SN - 1868-8551 VL - 32 IS - 4 SP - 297 EP - 306 PB - Springer CY - Heidelberg ER - TY - JOUR A1 - Pathe-Neuschäfer-Rube, Andrea A1 - Neuschäfer-Rube, Frank A1 - Haas, Gerald A1 - Langoth-Fehringer, Nina A1 - Püschel, Gerhard Paul T1 - Cell-Based Reporter Release Assay to Determine the Potency of Proteolytic Bacterial Neurotoxins JF - Toxins N2 - Despite the implementation of cell-based replacement methods, the mouse lethality assay is still frequently used to determine the activity of botulinum toxin (BoNT) for medical use. One explanation is that due to the use of neoepitope-specific antibodies to detect the cleaved BoNT substrate, the currently devised assays can detect only one specific serotype of the toxin. Recently, we developed a cell-based functional assay, in which BoNT activity is determined by inhibiting the release of a reporter enzyme that is liberated concomitantly with the neurotransmitter from neurosecretory vesicles. In theory, this assay should be suitable to detect the activity of any BoNT serotype. Consistent with this assumption, the current study shows that the stimulus-dependent release of a luciferase from a differentiated human neuroblastoma-based reporter cell line (SIMA-hPOMC1-26-GLuc cells) was inhibited by BoNT-A and-C. Furthermore, this was also inhibited by BoNT-B and tetanus toxin to a lesser extent and at higher concentrations. In order to provide support for the suitability of this technique in practical applications, a dose–response curve obtained with a pharmaceutical preparation of BoNT-A closely mirrored the activity determined in the mouse lethality assay. In summary, the newly established cell-based assay may represent a versatile and specific alternative to the mouse lethality assay and other currently established cell-based assays. KW - botulinum toxin KW - BoNT KW - tetanus toxin KW - RRR KW - replacement Y1 - 2018 U6 - https://doi.org/10.3390/toxins10090360 SN - 2072-6651 VL - 10 IS - 9 SP - 1 EP - 10 PB - Molecular Diversity Preservation International (MDPI) CY - Basel ER - TY - JOUR A1 - Pathe-Neuschäfer-Rube, Andrea A1 - Neuschäfer-Rube, Frank A1 - Püschel, Gerhard Paul T1 - Role of the ERC motif in the proximal part of the second intracellular loop and the C-terminal domain of the human prostaglandin F2alpha receptor (hFP-R) in G-protein coupling control N2 - The human FP-R (F2alpha prostaglandin receptor) is a Gq-coupled heptahelical ectoreceptor, which is of significant medical interest, since it is a potential target for the treatment of glaucoma and preterm labour. On agonist exposure, it mediates an increase in intracellular inositol phosphate formation. Little is known about the structures that govern the agonist-dependent receptor activation. In other prostanoid receptors, the C-terminal domain has been inferred in the control of agonist-dependent receptor activation. A DRY motif at the beginning of the second intracellular loop is highly conserved throughout the G-protein-coupled receptor family and appears to be crucial for controlling agonist-dependent receptor activation. It is replaced by an ERC motif in the FP-R and no evidence for the relevance of this motif in ligand-dependent activation of prostanoid receptors has been provided so far. The aim of the present study was to elucidate the potential role of the C-terminal domain and the ERC motif in agonist-controlled intracellular signalling in FP-R mutants generated by site-directed mutagenesis. It was found that substitution of the acidic Glu(132) in the ERC motif by a threonine residue led to full constitutive activation, whereas truncation of the receptor's C-terminal domain led to partial constitutive activation of all three intracellular signal pathways that had previously been shown to be activated by the FP-R, i.e. inositol trisphosphate formation, focal adhesion kinase activation and T-cell factor signalling. Inositol trisphosphate formation and focal adhesion kinase phosphorylation were further enhanced by ligand binding in cells expressing the truncation mutant but not the E132T (Glu132-->Thr) mutant. Thus C-terminal truncation appeared to result in a receptor with partial constitutive activation, whereas substitution of Glu132 by threonine apparently resulted in a receptor with full constitutive activity. Y1 - 2005 UR - http://www.biochemj.org/bj/388/0317/bj3880317.htm ER - TY - JOUR A1 - Neuschäfer-Rube, Frank A1 - Hermosilla, Ricardo A1 - Kuna, Manuela A1 - Pathe-Neuschäfer-Rube, Andrea A1 - Schulein, R. A1 - Püschel, Gerhard Paul T1 - A Ser/Thr cluster within the C-terminal domain of the rat prostaglandin receptor EP3 alpha is essential for agonist-induced phosphorylation, desensitization and internalization N2 - 1 Two isoforms of the rat prostaglandin E-2 receptor, rEP3 alpha-R and rEP3 beta-R, differ only in their C- terminal domain. To analyze the function of the rEP3-R C-terminal domain in agonist induced desensitization, a cluster of Ser/Thr residues in the C-terminal domain of the rEP3 alpha-R was mutated to Ala and both isoforms and the receptor mutant (rEP3 alpha-ST341-349A-R) were stably expressed in HEK293 cells. 2 All rEP3-R receptors showed a similar ligand- binding profile. They were functionally coupled to Gi and reduced forskolin-induced cAMP-formation. 3 Repeated exposure of cells expressing the rEP3 alpha-R isoform to PGE(2) reduced the agonist induced inhibition of forskolin-stimulated cAMP-formation by 50% and led to internalization of the receptor to intracellular endocytotic vesicles. By contrast, Gi- response as well as plasma membrane localization of the rEP3 beta-R and the rEP3 alpha-ST341-349A-R were not affected by prior agonist-stimulation. 4 Agonist-stimulation of HEK293-rEP3 alpha-R cells induced a time- and dose-dependent phosphorylation of the receptor most likely by G protein-coupled receptor kinases and not by protein kinase A or protein kinase C. By contrast, upon agonist-stimulation the rEP3 beta-R was not phosphorylated and the rEP3 alpha-ST341-349A-R was phosphorylated only weakly. 5 These results led to the hypothesis that agonist-induced desensitization of the rEP3 alpha-R isoform is mediated most likely by a GRK-dependent phosphorylation of Ser/Thr residues 341 - 349. Phosphorylation then initiates uncoupling of the receptor from Gi protein and receptor internalization Y1 - 2005 SN - 0007-1188 ER - TY - JOUR A1 - Pathe-Neuschäfer-Rube, Andrea A1 - Neuschäfer-Rube, Frank A1 - Püschel, Gerhard Paul T1 - G protein coupling control by the ERC-motif in the proximal part of the second intracellular loop and the C- terminal domain of the human prostaglandin F-2A receptor (FP receptor) Y1 - 2004 SN - 0028-1298 ER - TY - JOUR A1 - Neuschäfer-Rube, Frank A1 - Hermosilla, Ricardo A1 - Kuna, Manuela A1 - Pathe-Neuschaefer-Rube, Andrea A1 - Püschel, Gerhard Paul T1 - Agonist-induced desensitization of rat prostaglandin EP3 receptor isoforms Y1 - 2004 SN - 0028-1298 ER - TY - JOUR A1 - Neuschaefer-Rube, Frank A1 - Lieske, Stefanie A1 - Kuna, Manuela A1 - Henkel, Janin A1 - Perry, Rachel J. A1 - Erion, Derek M. A1 - Pesta, Dominik A1 - Willmes, Diana M. A1 - Brachs, Sebastian A1 - von Loeffelholz, Christian A1 - Tolkachov, Alexander A1 - Schupp, Michael A1 - Pathe-Neuschaefer-Rube, Andrea A1 - Pfeiffer, Andreas F. H. A1 - Shulman, Gerald I. A1 - Püschel, Gerhard Paul A1 - Birkenfeld, Andreas L. T1 - The mammalian INDY homolog is induced by CREB in a rat model of type 2 diabetes JF - Diabetes : a journal of the American Diabetes Association Y1 - 2014 SN - 0012-1797 SN - 1939-327X VL - 63 IS - 3 SP - 1048 EP - 1057 PB - American Diabetes Association CY - Alexandria ER - TY - JOUR A1 - Neuschäfer-Rube, Frank A1 - Pathe-Neuschäfer-Rube, Andrea A1 - Püschel, Gerhard Paul T1 - Discrimination of the activity of low-affinity wild-type and high-affinity mutant recombinant BoNT/B by a SIMA cell-based reporter release assay JF - Toxins N2 - Botulinum neurotoxin (BoNT) is used for the treatment of a number of ailments. The activity of the toxin that is isolated from bacterial cultures is frequently tested in the mouse lethality assay. Apart from the ethical concerns inherent to this assay, species-specific differences in the affinity for different BoNT serotypes give rise to activity results that differ from the activity in humans. Thus, BoNT/B is more active in mice than in humans. The current study shows that the stimulus-dependent release of a luciferase from a differentiated human neuroblastoma–based reporter cell line (SIMA-hPOMC1-26-Gluc) was inhibited by clostridial and recombinant BoNT/A to the same extent, whereas both clostridial and recombinant BoNT/B inhibited the release to a lesser extent and only at much higher concentrations, reflecting the low activity of BoNT/B in humans. By contrast, the genetically modified BoNT/B-MY, which has increased affinity for human synaptotagmin, and the BoNT/B protein receptor inhibited luciferase release effectively and with an EC50 comparable to recombinant BoNT/A. This was due to an enhanced uptake into the reporter cells of BoNT/B-MY in comparison to the recombinant wild-type toxin. Thus, the SIMA-hPOMC1-26-Gluc cell assay is a versatile tool to determine the activity of different BoNT serotypes providing human-relevant dose-response data. KW - cell-based assay KW - genetically modified BoNT KW - BoNT/B uptake Y1 - 2022 U6 - https://doi.org/10.3390/toxins14010065 SN - 2072-6651 VL - 14 SP - 1 EP - 11 PB - MDPI CY - Basel, Schweiz ET - 1 ER - TY - JOUR A1 - Neuschäfer-Rube, Frank A1 - Pathe-Neuschäfer-Rube, Andrea A1 - Hippenstiel, Stefan A1 - Püschel, Gerhard Paul T1 - PGE(2) enhanced TNF alpha-mediated IL-8 induction in monocytic cell lines and PBMC JF - Cytokine N2 - Background & purpose: Recent studies suggested a role of prostaglandin E-2 (PGE(2)) in the expression of the chemokine IL-8 by monocytes. The function of EP4 receptor for TNF alpha-induced IL-8 expression was studied in monocytic cell lines. Experimental approach: IL-8 mRNA and protein induction as well as IL-8 promoter activity and transcription factor activation were assessed in monocytic cell lines, primary blood mononuclear cells (PBMC) and transgenic HEK293 cells expressing the EP4 receptor. Key results: In monocytic cell lines THP-1, MonoMac and U937 PGE(2) had only a marginal impact on IL-8 induction but strongly enhanced TNFa-induced IL-8 mRNA and protein synthesis. Similarly, in PBMC IL-8 mRNA induction was larger by simultaneous stimulation with TNF alpha and PGE(2) than by either stimulus alone. The EP4 receptor subtype was the most abundant EP receptor in all three cell lines and in PBMC. Stimulation of THP-1 cells with an EP4 specific agonist enhanced TNF alpha-induced IL-8 mRNA and protein formation to the same extent as PGE(2). In HEK293 cells expressing EP4, but not in wild type HEK293 cells lacking EP4, PGE(2) enhanced TNFainduced IL-8 protein and mRNA synthesis. In THP-1 cells, the enhancement of TNF alpha-mediated IL-8 mRNA induction by PGE(2) was mimicked by a PICA-activator. Furthermore in these cells PGE(2) induced expression of transcription factor C/EBPS, enhanced NF-KB activation by TNFa and inhibited TNF alpha-mediated AP-1 activation. PGE(2) and TNF alpha synergistically activated transcription factor CREB, induced C/EBPS expression and enhanced the activity of an IL-8 promoter fragment containing-223 bp upstream of the transcription start site. Conclusions and implications: These findings suggest that a combined stimulation of TNF alpha and PGE(2)/EP4 signal chains in monocytic cells leads to maximal IL-8 promoter activity, as well as IL-8 mRNA and protein induction, by activating the PICA/CREB/C/EB1313 as well as NF-kappa B signal chains. KW - Monocyte KW - Prostaglandin receptor EP4 KW - IL-8 transcription KW - Signal transduction KW - Tumor necrosis factor alpha Y1 - 2018 U6 - https://doi.org/10.1016/j.cyto.2018.06.020 SN - 1043-4666 SN - 1096-0023 VL - 113 SP - 105 EP - 116 PB - Elsevier CY - London ER - TY - JOUR A1 - Pathe-Neuschäfer-Rube, Andrea A1 - Neuschäfer-Rube, Frank A1 - Püschel, Gerhard Paul T1 - Cell-based reporter release assay to determine the activity of calcium-dependent neurotoxins and neuroactive pharmaceuticals JF - Toxins / Molecular Diversity Preservation International (MDPI) N2 - The suitability of a newly developed cell-based functional assay was tested for the detection of the activity of a range of neurotoxins and neuroactive pharmaceuticals which act by stimulation or inhibition of calcium-dependent neurotransmitter release. In this functional assay, a reporter enzyme is released concomitantly with the neurotransmitter from neurosecretory vesicles. The current study showed that the release of a luciferase from a differentiated human neuroblastoma-based reporter cell line (SIMA-hPOMC1-26-GLuc cells) can be stimulated by a carbachol-mediated activation of the Gq-coupled muscarinic-acetylcholine receptor and by the Ca2+-channel forming spider toxin α-latrotoxin. Carbachol-stimulated luciferase release was completely inhibited by the muscarinic acetylcholine receptor antagonist atropine and α-latrotoxin-mediated release by the Ca2+-chelator EGTA, demonstrating the specificity of luciferase-release stimulation. SIMA-hPOMC1-26-GLuc cells express mainly L- and N-type and to a lesser extent T-type VGCC on the mRNA and protein level. In accordance with the expression profile a depolarization-stimulated luciferase release by a high K+-buffer was effectively and dose-dependently inhibited by L-type VGCC inhibitors and to a lesser extent by N-type and T-type inhibitors. P/Q- and R-type inhibitors did not affect the K+-stimulated luciferase release. In summary, the newly established cell-based assay may represent a versatile tool to analyze the biological efficiency of a range of neurotoxins and neuroactive pharmaceuticals which mediate their activity by the modulation of calcium-dependent neurotransmitter release. KW - cell-based assay KW - neurotoxins KW - muscarinic acetylcholine receptor KW - voltage-dependent calcium channels KW - VGCC Y1 - 2021 U6 - https://doi.org/10.3390/toxins13040247 SN - 2072-6651 VL - 13 IS - 4 PB - MDPI CY - Basel ER - TY - GEN A1 - Pathe-Neuschäfer-Rube, Andrea A1 - Neuschäfer-Rube, Frank A1 - Püschel, Gerhard Paul T1 - Cell-based reporter release assay to determine the activity of calcium-dependent neurotoxins and neuroactive pharmaceuticals T2 - Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe N2 - The suitability of a newly developed cell-based functional assay was tested for the detection of the activity of a range of neurotoxins and neuroactive pharmaceuticals which act by stimulation or inhibition of calcium-dependent neurotransmitter release. In this functional assay, a reporter enzyme is released concomitantly with the neurotransmitter from neurosecretory vesicles. The current study showed that the release of a luciferase from a differentiated human neuroblastoma-based reporter cell line (SIMA-hPOMC1-26-GLuc cells) can be stimulated by a carbachol-mediated activation of the Gq-coupled muscarinic-acetylcholine receptor and by the Ca2+-channel forming spider toxin α-latrotoxin. Carbachol-stimulated luciferase release was completely inhibited by the muscarinic acetylcholine receptor antagonist atropine and α-latrotoxin-mediated release by the Ca2+-chelator EGTA, demonstrating the specificity of luciferase-release stimulation. SIMA-hPOMC1-26-GLuc cells express mainly L- and N-type and to a lesser extent T-type VGCC on the mRNA and protein level. In accordance with the expression profile a depolarization-stimulated luciferase release by a high K+-buffer was effectively and dose-dependently inhibited by L-type VGCC inhibitors and to a lesser extent by N-type and T-type inhibitors. P/Q- and R-type inhibitors did not affect the K+-stimulated luciferase release. In summary, the newly established cell-based assay may represent a versatile tool to analyze the biological efficiency of a range of neurotoxins and neuroactive pharmaceuticals which mediate their activity by the modulation of calcium-dependent neurotransmitter release. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 1139 KW - cell-based assay KW - neurotoxins KW - muscarinic acetylcholine receptor KW - voltage-dependent calcium channels KW - VGCC Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-503225 SN - 1866-8372 IS - 1139 ER - TY - GEN A1 - Neuschäfer-Rube, Frank A1 - Pathe-Neuschäfer-Rube, Andrea A1 - Püschel, Gerhard Paul T1 - Discrimination of the Activity of Low-Affinity Wild-Type and High-Affinity Mutant Recombinant BoNT/B by a SIMA Cell-Based Reporter Release Assay T2 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe N2 - Botulinum neurotoxin (BoNT) is used for the treatment of a number of ailments. The activity of the toxin that is isolated from bacterial cultures is frequently tested in the mouse lethality assay. Apart from the ethical concerns inherent to this assay, species-specific differences in the affinity for different BoNT serotypes give rise to activity results that differ from the activity in humans. Thus, BoNT/B is more active in mice than in humans. The current study shows that the stimulus-dependent release of a luciferase from a differentiated human neuroblastoma–based reporter cell line (SIMA-hPOMC1-26-Gluc) was inhibited by clostridial and recombinant BoNT/A to the same extent, whereas both clostridial and recombinant BoNT/B inhibited the release to a lesser extent and only at much higher concentrations, reflecting the low activity of BoNT/B in humans. By contrast, the genetically modified BoNT/B-MY, which has increased affinity for human synaptotagmin, and the BoNT/B protein receptor inhibited luciferase release effectively and with an EC50 comparable to recombinant BoNT/A. This was due to an enhanced uptake into the reporter cells of BoNT/B-MY in comparison to the recombinant wild-type toxin. Thus, the SIMA-hPOMC1-26-Gluc cell assay is a versatile tool to determine the activity of different BoNT serotypes providing human-relevant dose-response data. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 1257 KW - cell-based assay KW - genetically modified BoNT KW - BoNT/B uptake Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-558032 SN - 1866-8372 SP - 1 EP - 11 PB - Universitätsverlag Potsdam CY - Potsdam ER - TY - JOUR A1 - Renteria, Miguel E. A1 - Schmaal, L. A1 - Hibar, D. P. A1 - Couvy-Duchesne, B. A1 - Strike, L. T. A1 - Mills, N. T. A1 - de Zubicaray, Greig. I. A1 - McMahon, Katie. L. A1 - Medland, Sarah E. A1 - Gillespie, N. A. A1 - Hatton, S. N. A1 - Lagopoulos, J. A1 - Veltman, D. J. A1 - van der Wee, N. A1 - van Erp, T. G. M. A1 - Wittfeld, K. A1 - Grabe, H. J. A1 - Block, Andrea A1 - Hegenscheid, K. A1 - Voelzke, H. A1 - Veer, I. M. A1 - Walter, H. A1 - Schnell, K. A1 - Schramm, E. A1 - Normann, C. A1 - Schoepf, Dieter A1 - Konrad, C. A1 - Zurowski, B. A1 - Godlewska, B. R. A1 - Cowen, P. J. A1 - Penninx, B. W. J. H. A1 - Jahanshad, N. A1 - Thompson, Paul M. A1 - Wright, M. J. A1 - Martin, N. G. A1 - Christensen, H. A1 - Hickie, I. B. T1 - Subcortical brain structure and suicidal behaviour in major depressive disorder: a meta-analysis from the ENIGMA-MDD working group JF - Translational Psychiatry Y1 - 2017 U6 - https://doi.org/10.1038/tp.2017.84 SN - 2158-3188 VL - 7 SP - 2301 EP - 2320 PB - Nature Publ. Group CY - New York ER - TY - JOUR A1 - Weber, Michael H. A1 - Abu-Ayyash, Khalil A1 - Abueladas, Abdel-Rahman A1 - Agnon, Amotz A1 - Alasonati-Tašárová, Zuzana A1 - Al-Zubi, Hashim A1 - Babeyko, Andrey A1 - Bartov, Yuval A1 - Bauer, Klaus A1 - Becken, Michael A1 - Bedrosian, Paul A. A1 - Ben-Avraham, Zvi A1 - Bock, Günter A1 - Bohnhoff, Marco A1 - Bribach, Jens A1 - Dulski, Peter A1 - Ebbing, Joerg A1 - El-Kelani, Radwan J. A1 - Foerster, Andrea A1 - Förster, Hans-Jürgen A1 - Frieslander, Uri A1 - Garfunkel, Zvi A1 - Götze, Hans-Jürgen A1 - Haak, Volker A1 - Haberland, Christian A1 - Hassouneh, Mohammed A1 - Helwig, Stefan L. A1 - Hofstetter, Alfons A1 - Hoffmann-Rothe, Arne A1 - Jaeckel, Karl-Heinz A1 - Janssen, Christoph A1 - Jaser, Darweesh A1 - Kesten, Dagmar A1 - Khatib, Mohammed Ghiath A1 - Kind, Rainer A1 - Koch, Olaf A1 - Koulakov, Ivan A1 - Laske, Maria Gabi A1 - Maercklin, Nils T1 - Anatomy of the Dead Sea transform from lithospheric to microscopic scale N2 - Fault zones are the locations where motion of tectonic plates, often associated with earthquakes, is accommodated. Despite a rapid increase in the understanding of faults in the last decades, our knowledge of their geometry, petrophysical properties, and controlling processes remains incomplete. The central questions addressed here in our study of the Dead Sea Transform (DST) in the Middle East are as follows: (1) What are the structure and kinematics of a large fault zone? (2) What controls its structure and kinematics? (3) How does the DST compare to other plate boundary fault zones? The DST has accommodated a total of 105 km of left-lateral transform motion between the African and Arabian plates since early Miocene (similar to 20 Ma). The DST segment between the Dead Sea and the Red Sea, called the Arava/Araba Fault (AF), is studied here using a multidisciplinary and multiscale approach from the mu m to the plate tectonic scale. We observe that under the DST a narrow, subvertical zone cuts through crust and lithosphere. First, from west to east the crustal thickness increases smoothly from 26 to 39 km, and a subhorizontal lower crustal reflector is detected east of the AF. Second, several faults exist in the upper crust in a 40 km wide zone centered on the AF, but none have kilometer-size zones of decreased seismic velocities or zones of high electrical conductivities in the upper crust expected for large damage zones. Third, the AF is the main branch of the DST system, even though it has accommodated only a part (up to 60 km) of the overall 105 km of sinistral plate motion. Fourth, the AF acts as a barrier to fluids to a depth of 4 km, and the lithology changes abruptly across it. Fifth, in the top few hundred meters of the AF a locally transpressional regime is observed in a 100-300 m wide zone of deformed and displaced material, bordered by subparallel faults forming a positive flower structure. Other segments of the AF have a transtensional character with small pull-aparts along them. The damage zones of the individual faults are only 5-20 m wide at this depth range. Sixth, two areas on the AF show mesoscale to microscale faulting and veining in limestone sequences with faulting depths between 2 and 5 km. Seventh, fluids in the AF are carried downward into the fault zone. Only a minor fraction of fluids is derived from ascending hydrothermal fluids. However, we found that on the kilometer scale the AF does not act as an important fluid conduit. Most of these findings are corroborated using thermomechanical modeling where shear deformation in the upper crust is localized in one or two major faults; at larger depth, shear deformation occurs in a 20-40 km wide zone with a mechanically weak decoupling zone extending subvertically through the entire lithosphere. Y1 - 2009 UR - http://www.agu.org/journals/rg/ U6 - https://doi.org/10.1029/2008rg000264 SN - 8755-1209 ER - TY - JOUR A1 - Khudair, Mohammed A1 - Marcuzzi, Anna A1 - Ng, Kwok A1 - Tempest, Gavin Daniel A1 - Bartoš, František A1 - Peric, Ratko A1 - Maier, Maximilian A1 - Beccia, Flavia A1 - Boccia, Stefania A1 - Brandes, Mirko A1 - Cardon, Greet A1 - Carlin, Angela A1 - Castagna, Carolina A1 - Chaabene, Helmi A1 - Chalkley, Anna A1 - Ciaccioni, Simone A1 - Cieślińska-Świder, Joanna A1 - Čingienė, Vilma A1 - Cortis, Cristina A1 - Corvino, Chiara A1 - de Geus, Eco J. C. A1 - Di Baldassarre, Angela A1 - Di Credico, Andrea A1 - Drid, Patrik A1 - Tarazaga, Rosa Ma Fernández A1 - Gallè, Francesca A1 - Sánchez, Esther Garcia A1 - Gebremariam, Mekdes A1 - Ghinassi, Barbara A1 - Goudas, Marios A1 - Hayes, Grainne A1 - Honorio, Samuel A1 - Izzicupo, Pascal A1 - Jahre, Henriette A1 - Jelsma, Judith A1 - Juric, Petra A1 - Kolovelonis, Athanasios A1 - Kongsvold, Atle A1 - Kouidi, Evangelia A1 - Mansergh, Fiona A1 - Masanovic, Bojan A1 - Mekonnen, Teferi A1 - Mork, Paul Jarle A1 - Murphy, Marie A1 - O'Hara, Kelly A1 - Torun, Ayse Ozbil A1 - Palumbo, Federico A1 - Popovic, Stevo A1 - Prieske, Olaf A1 - Puharic, Zrinka A1 - Ribeiro, José Carlos A1 - Rumbold, Penny Louise Sheena A1 - Sandu, Petru A1 - Soric, Maroje A1 - Stavnsbo, Mette A1 - Syrmpas, Ioannis A1 - van der Ploeg, Hidde P. A1 - Van Hoye, Aurélie A1 - Vilela, Sofia A1 - Woods, Catherine A1 - Wunsch, Kathrin A1 - Caprinica, Laura A1 - MacDonncha, Ciaran A1 - Ling, Fiona Chun Man T1 - DE-PASS Best Evidence Statement (BESt): modifiable determinants of physical activity and sedentary behaviour in children and adolescents aged 5-19 years-a protocol for systematic review and meta-analysis JF - BMJ open N2 - Introduction Physical activity among children and adolescents remains insufficient, despite the substantial efforts made by researchers and policymakers. Identifying and furthering our understanding of potential modifiable determinants of physical activity behaviour (PAB) and sedentary behaviour (SB) is crucial for the development of interventions that promote a shift from SB to PAB. The current protocol details the process through which a series of systematic literature reviews and meta-analyses (MAs) will be conducted to produce a best-evidence statement (BESt) and inform policymakers. The overall aim is to identify modifiable determinants that are associated with changes in PAB and SB in children and adolescents (aged 5-19 years) and to quantify their effect on, or association with, PAB/SB. Methods and analysis A search will be performed in MEDLINE, SportDiscus, Web of Science, PsychINFO and Cochrane Central Register of Controlled Trials. Randomised controlled trials (RCTs) and controlled trials (CTs) that investigate the effect of interventions on PAB/SB and longitudinal studies that investigate the associations between modifiable determinants and PAB/SB at multiple time points will be sought. Risk of bias assessments will be performed using adapted versions of Cochrane's RoB V.2.0 and ROBINS-I tools for RCTs and CTs, respectively, and an adapted version of the National Institute of Health's tool for longitudinal studies. Data will be synthesised narratively and, where possible, MAs will be performed using frequentist and Bayesian statistics. Modifiable determinants will be discussed considering the settings in which they were investigated and the PAB/SB measurement methods used. Ethics and dissemination No ethical approval is needed as no primary data will be collected. The findings will be disseminated in peer-reviewed publications and academic conferences where possible. The BESt will also be shared with policy makers within the DE-PASS consortium in the first instance. Systematic review registration CRD42021282874. KW - public health KW - health policy KW - community child health Y1 - 2022 U6 - https://doi.org/10.1136/bmjopen-2021-059202 SN - 2044-6055 VL - 12 IS - 9 PB - BMJ Publishing Group CY - London ER - TY - JOUR A1 - Diercke, Andrea A1 - Kuckein, Christoph A1 - Cauley, Paul Wilson A1 - Poppenhäger, Katja A1 - Alvarado-Gómez, Julián David A1 - Dineva, Ekaterina Ivanova A1 - Denker, Carsten T1 - Solar H alpha excess during Solar Cycle 24 from full-disk filtergrams of the Chromospheric Telescope JF - Astronomy and astrophysics : an international weekly journal N2 - Context The chromospheric H alpha spectral line is a strong line in the spectrum of the Sun and other stars. In the stellar regime, this spectral line is already used as a powerful tracer of stellar activity. For the Sun, other tracers, such as Ca II K, are typically used to monitor solar activity. Nonetheless, the Sun is observed constantly in H alpha with globally distributed ground-based full-disk imagers. Aims The aim of this study is to introduce the imaging H alpha excess and deficit as tracers of solar activity and compare them to other established indicators. Furthermore, we investigate whether the active region coverage fraction or the changing H alpha excess in the active regions dominates temporal variability in solar H alpha observations. Methods We used observations of full-disk H alpha filtergrams of the Chromospheric Telescope and morphological image processing techniques to extract the imaging H alpha excess and deficit, which were derived from the intensities above or below 10% of the median intensity in the filtergrams, respectively. These thresholds allowed us to filter for bright features (plage regions) and dark absorption features (filaments and sunspots). In addition, the thresholds were used to calculate the mean intensity I-mean(E/D) for H alpha excess and deficit regions. We describe the evolution of the H alpha excess and deficit during Solar Cycle 24 and compare it to the mean intensity and other well established tracers: the relative sunspot number, the F10.7 cm radio flux, and the Mg II index. In particular, we tried to determine how constant the H alpha excess and number density of H alpha excess regions are between solar maximum and minimum. The number of pixels above or below the intensity thresholds were used to calculate the area coverage fraction of H alpha excess and deficit regions on the Sun, which was compared to the imaging H alpha excess and deficit and the respective mean intensities averaged for the length of one Carrington rotation. In addition, we present the H alpha excess and mean intensity variation of selected active regions during their disk passage in comparison to the number of pixels of H alpha excess regions. Results. The H alpha excess and deficit follow the behavior of the solar activity over the course of the cycle. They both peak around solar maximum, whereby the peak of the H alpha deficit is shortly after the solar maximum. Nonetheless, the correlation of the monthly averages of the H alpha excess and deficit is high with a Spearman correlation of rho =  0.91. The H alpha excess is closely correlated to the chromospheric Mg II index with a correlation of 0.95. The highest correlation of the H alpha deficit is found with the F10.7 cm radio flux, with a correlation of 0.89, due to their peaks after the solar activity maximum. Furthermore, the H alpha deficit reflects the cyclic behavior of polar crown filaments and their disappearance shortly before the solar maximum. We investigated the mean intensity distribution for H alpha excess regions for solar minimum and maximum. The shape of the distributions for solar minimum and maximum is very similar, but with different amplitudes. Furthermore, we found that the area coverage fraction of H alpha excess regions and the H alpha excess are strongly correlated with an overall Spearman correlation of 0.92. The correlation between the H alpha excess and the mean intensity of H alpha excess regions is 0.75. The correlation of the area coverage fraction and the mean intensity of H alpha excess regions is in general relatively low (rho = 0.45) and only for few active regions is this correlation above 0.7. The weak correlation between the area coverage fraction and mean intensity leaves us pessimistic that the degeneracy between these two quantities can be broken for the modeling of unresolved stellar surfaces. KW - methods: observational KW - Sun: chromosphere KW - Sun: activity KW - Sun: faculae, plages KW - Sun: filaments KW - stars: atmospheres KW - prominences Y1 - 2022 U6 - https://doi.org/10.1051/0004-6361/202040091 SN - 1432-0746 SN - 0004-6361 VL - 661 PB - EDP Sciences CY - Les Ulis ER - TY - BOOK A1 - Kuban, Robert A1 - Rotta, Randolf A1 - Nolte, Jörg A1 - Chromik, Jonas A1 - Beilharz, Jossekin Jakob A1 - Pirl, Lukas A1 - Friedrich, Tobias A1 - Lenzner, Pascal A1 - Weyand, Christopher A1 - Juiz, Carlos A1 - Bermejo, Belen A1 - Sauer, Joao A1 - Coelh, Leandro dos Santos A1 - Najafi, Pejman A1 - Pünter, Wenzel A1 - Cheng, Feng A1 - Meinel, Christoph A1 - Sidorova, Julia A1 - Lundberg, Lars A1 - Vogel, Thomas A1 - Tran, Chinh A1 - Moser, Irene A1 - Grunske, Lars A1 - Elsaid, Mohamed Esameldin Mohamed A1 - Abbas, Hazem M. A1 - Rula, Anisa A1 - Sejdiu, Gezim A1 - Maurino, Andrea A1 - Schmidt, Christopher A1 - Hügle, Johannes A1 - Uflacker, Matthias A1 - Nozza, Debora A1 - Messina, Enza A1 - Hoorn, André van A1 - Frank, Markus A1 - Schulz, Henning A1 - Alhosseini Almodarresi Yasin, Seyed Ali A1 - Nowicki, Marek A1 - Muite, Benson K. A1 - Boysan, Mehmet Can A1 - Bianchi, Federico A1 - Cremaschi, Marco A1 - Moussa, Rim A1 - Abdel-Karim, Benjamin M. A1 - Pfeuffer, Nicolas A1 - Hinz, Oliver A1 - Plauth, Max A1 - Polze, Andreas A1 - Huo, Da A1 - Melo, Gerard de A1 - Mendes Soares, Fábio A1 - Oliveira, Roberto Célio Limão de A1 - Benson, Lawrence A1 - Paul, Fabian A1 - Werling, Christian A1 - Windheuser, Fabian A1 - Stojanovic, Dragan A1 - Djordjevic, Igor A1 - Stojanovic, Natalija A1 - Stojnev Ilic, Aleksandra A1 - Weidmann, Vera A1 - Lowitzki, Leon A1 - Wagner, Markus A1 - Ifa, Abdessatar Ben A1 - Arlos, Patrik A1 - Megia, Ana A1 - Vendrell, Joan A1 - Pfitzner, Bjarne A1 - Redondo, Alberto A1 - Ríos Insua, David A1 - Albert, Justin Amadeus A1 - Zhou, Lin A1 - Arnrich, Bert A1 - Szabó, Ildikó A1 - Fodor, Szabina A1 - Ternai, Katalin A1 - Bhowmik, Rajarshi A1 - Campero Durand, Gabriel A1 - Shevchenko, Pavlo A1 - Malysheva, Milena A1 - Prymak, Ivan A1 - Saake, Gunter ED - Meinel, Christoph ED - Polze, Andreas ED - Beins, Karsten ED - Strotmann, Rolf ED - Seibold, Ulrich ED - Rödszus, Kurt ED - Müller, Jürgen T1 - HPI Future SOC Lab – Proceedings 2019 N2 - The “HPI Future SOC Lab” is a cooperation of the Hasso Plattner Institute (HPI) and industry partners. Its mission is to enable and promote exchange and interaction between the research community and the industry partners. The HPI Future SOC Lab provides researchers with free of charge access to a complete infrastructure of state of the art hard and software. This infrastructure includes components, which might be too expensive for an ordinary research environment, such as servers with up to 64 cores and 2 TB main memory. The offerings address researchers particularly from but not limited to the areas of computer science and business information systems. Main areas of research include cloud computing, parallelization, and In-Memory technologies. This technical report presents results of research projects executed in 2019. Selected projects have presented their results on April 9th and November 12th 2019 at the Future SOC Lab Day events. N2 - Das Future SOC Lab am HPI ist eine Kooperation des Hasso-Plattner-Instituts mit verschiedenen Industriepartnern. Seine Aufgabe ist die Ermöglichung und Förderung des Austausches zwischen Forschungsgemeinschaft und Industrie. Am Lab wird interessierten Wissenschaftlern eine Infrastruktur von neuester Hard- und Software kostenfrei für Forschungszwecke zur Verfügung gestellt. Dazu zählen teilweise noch nicht am Markt verfügbare Technologien, die im normalen Hochschulbereich in der Regel nicht zu finanzieren wären, bspw. Server mit bis zu 64 Cores und 2 TB Hauptspeicher. Diese Angebote richten sich insbesondere an Wissenschaftler in den Gebieten Informatik und Wirtschaftsinformatik. Einige der Schwerpunkte sind Cloud Computing, Parallelisierung und In-Memory Technologien. In diesem Technischen Bericht werden die Ergebnisse der Forschungsprojekte des Jahres 2019 vorgestellt. Ausgewählte Projekte stellten ihre Ergebnisse am 09. April und 12. November 2019 im Rahmen des Future SOC Lab Tags vor. T3 - Technische Berichte des Hasso-Plattner-Instituts für Digital Engineering an der Universität Potsdam - 158 KW - Future SOC Lab KW - research projects KW - multicore architectures KW - in-memory technology KW - cloud computing KW - machine learning KW - artifical intelligence KW - Future SOC Lab KW - Forschungsprojekte KW - Multicore Architekturen KW - In-Memory Technologie KW - Cloud Computing KW - maschinelles Lernen KW - künstliche Intelligenz Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-597915 SN - 978-3-86956-564-4 SN - 1613-5652 SN - 2191-1665 IS - 158 PB - Universitätsverlag Potsdam CY - Potsdam ER - TY - JOUR A1 - Leunert, Franziska A1 - Eckert, Werner A1 - Paul, Andrea A1 - Gerhardt, Volkmar A1 - Grossart, Hans-Peter T1 - Phytoplankton response to UV-generated hydrogen peroxide from natural organic matter JF - Journal of plankton research N2 - In aquatic systems, natural organic matter (NOM) and in particular humic substances effectively absorb the ultraviolet (UV)/visible light spectrum of solar radiation and act as a photoprotective filter for organisms. Simultaneously, UV contributes to the generation of potentially harmful reactive oxygen species (ROS). Dose-response experiments were conducted on cyanobacteria and green algae with hydrogen peroxide (H2O2) as a long-lived representative of ROS. Delayed fluorescence (DF) decay kinetics was used as a non-invasive tool to follow changes of phytoplankton activity in real time. In order to investigate phototoxicity and photoprotection by NOM on phytoplankton, we exposed algae to UV-pre-irradiated NOM and direct UV excitation. Cyanobacteria responded to H2O2 concentrations as low as 10(-7) M, while green algae were 2 orders of magnitude less sensitive. UV irradiation of medium with NOM generated H2O2 concentrations of 1.5 x 10(-7) to 3.6 x 10(-7) M. When exposed to these concentrations, only the DF of cyanobacteria led to a measurable effect while that of green algae did not change. The addition of NOM protected all phytoplankton from direct UV irradiation, but cyanobacteria benefitted less. From this we conclude that UV-irradiated water enriched with NOM can adversely affect the physiology of cyanobacteria, but not of green algae, which might control phytoplankton composition and species-specific activities. KW - reactive oxygen species KW - Microcystis aeruginosa KW - green algae KW - delayed fluorescence KW - phycocyanin Y1 - 2014 U6 - https://doi.org/10.1093/plankt/fbt096 SN - 0142-7873 SN - 1464-3774 VL - 36 IS - 1 SP - 185 EP - 197 PB - Oxford Univ. Press CY - Oxford ER -