@article{TiegsCostelloIskenetal.2019,
  author    = {Tiegs, Scott D. and Costello, David M. and Isken, Mark W. and Woodward, Guy and McIntyre, Peter B. and Gessner, Mark O. and Chauvet, Eric and Griffiths, Natalie A. and Flecker, Alex S. and Acuna, Vicenc and Albarino, Ricardo and Allen, Daniel C. and Alonso, Cecilia and Andino, Patricio and Arango, Clay and Aroviita, Jukka and Barbosa, Marcus V. M. and Barmuta, Leon A. and Baxter, Colden V. and Bell, Thomas D. C. and Bellinger, Brent and Boyero, Luz and Brown, Lee E. and Bruder, Andreas and Bruesewitz, Denise A. and Burdon, Francis J. and Callisto, Marcos and Canhoto, Cristina and Capps, Krista A. and Castillo, Maria M. and Clapcott, Joanne and Colas, Fanny and Colon-Gaud, Checo and Cornut, Julien and Crespo-Perez, Veronica and Cross, Wyatt F. and Culp, Joseph M. and Danger, Michael and Dangles, Olivier and de Eyto, Elvira and Derry, Alison M. and Diaz Villanueva, Veronica and Douglas, Michael M. and Elosegi, Arturo and Encalada, Andrea C. and Entrekin, Sally and Espinosa, Rodrigo and Ethaiya, Diana and Ferreira, Veronica and Ferriol, Carmen and Flanagan, Kyla M. and Fleituch, Tadeusz and Shah, Jennifer J. Follstad and Frainer, Andre and Friberg, Nikolai and Frost, Paul C. and Garcia, Erica A. and Lago, Liliana Garcia and Garcia Soto, Pavel Ernesto and Ghate, Sudeep and Giling, Darren P. and Gilmer, Alan and Goncalves, Jose Francisco and Gonzales, Rosario Karina and Graca, Manuel A. S. and Grace, Mike and Grossart, Hans-Peter and Guerold, Francois and Gulis, Vlad and Hepp, Luiz U. and Higgins, Scott and Hishi, Takuo and Huddart, Joseph and Hudson, John and Imberger, Samantha and Iniguez-Armijos, Carlos and Iwata, Tomoya and Janetski, David J. and Jennings, Eleanor and Kirkwood, Andrea E. and Koning, Aaron A. and Kosten, Sarian and Kuehn, Kevin A. and Laudon, Hjalmar and Leavitt, Peter R. and Lemes da Silva, Aurea L. and Leroux, Shawn J. and Leroy, Carri J. and Lisi, Peter J. and MacKenzie, Richard and Marcarelli, Amy M. and Masese, Frank O. and Mckie, Brendan G. and Oliveira Medeiros, Adriana and Meissner, Kristian and Milisa, Marko and Mishra, Shailendra and Miyake, Yo and Moerke, Ashley and Mombrikotb, Shorok and Mooney, Rob and Moulton, Tim and Muotka, Timo and Negishi, Junjiro N. and Neres-Lima, Vinicius and Nieminen, Mika L. and Nimptsch, Jorge and Ondruch, Jakub and Paavola, Riku and Pardo, Isabel and Patrick, Christopher J. and Peeters, Edwin T. H. M. and Pozo, Jesus and Pringle, Catherine and Prussian, Aaron and Quenta, Estefania and Quesada, Antonio and Reid, Brian and Richardson, John S. and Rigosi, Anna and Rincon, Jose and Risnoveanu, Geta and Robinson, Christopher T. and Rodriguez-Gallego, Lorena and Royer, Todd V. and Rusak, James A. and Santamans, Anna C. and Selmeczy, Geza B. and Simiyu, Gelas and Skuja, Agnija and Smykla, Jerzy and Sridhar, Kandikere R. and Sponseller, Ryan and Stoler, Aaron and Swan, Christopher M. and Szlag, David and Teixeira-de Mello, Franco and Tonkin, Jonathan D. and Uusheimo, Sari and Veach, Allison M. and Vilbaste, Sirje and Vought, Lena B. M. and Wang, Chiao-Ping and Webster, Jackson R. and Wilson, Paul B. and Woelfl, Stefan and Xenopoulos, Marguerite A. and Yates, Adam G. and Yoshimura, Chihiro and Yule, Catherine M. and Zhang, Yixin X. and Zwart, Jacob A.},
  title     = {Global patterns and drivers of ecosystem functioning in rivers and riparian zones},
  series = {Science Advances},
  volume    = {5},
  journal   = {Science Advances},
  number    = {1},
  publisher = {American Assoc. for the Advancement of Science},
  address   = {Washington},
  issn      = {2375-2548},
  doi       = {10.1126/sciadv.aav0486},
  pages     = {8},
  year      = {2019},
  abstract  = {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.},
  language  = {en}
}
@article{vonLoeffelholzLieskeNeuschaeferRubeetal.2017,
  author    = {von Loeffelholz, Christian and Lieske, Stefanie and Neuschaefer-Rube, Frank and Willmes, Diana M. and Raschzok, Nathanael and Sauer, Igor M. and K{\"o}nig, J{\"o}rg and Fromm, Martin F. and Horn, Paul and Chatzigeorgiou, Antonios and Pathe-Neuschaefer-Rube, Andrea and Jordan, Jens and Pfeiffer, Andreas F. H. and Mingrone, Geltrude and Bornstein, Stefan R. and Stroehle, Peter and Harms, Christoph and Wunderlich, F. Thomas and Helfand, Stephen L. and Bernier, Michel and de Cabo, Rafael and Shulman, Gerald I. and Chavakis, Triantafyllos and P{\"u}schel, Gerhard Paul and Birkenfeld, Andreas L.},
  title     = {The human longevity gene homolog INDY and interleukin-6 interact in hepatic lipid metabolism},
  series = {Hepatology},
  volume    = {66},
  journal   = {Hepatology},
  number    = {2},
  publisher = {Wiley},
  address   = {Hoboken},
  issn      = {0270-9139},
  doi       = {10.1002/hep.29089},
  pages     = {616 -- 630},
  year      = {2017},
  abstract  = {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.},
  language  = {en}
}
@article{FrodlJanowitzSchmaaletal.2017,
  author    = {Frodl, Thomas and Janowitz, Deborah and Schmaal, Lianne and Tozzi, Leonardo and Dobrowolny, Henrik and Stein, Dan J. and Veltman, Dick J. and Wittfeld, Katharina and van Erp, Theo G. M. and Jahanshad, Neda and Block, Andrea and Hegenscheid, Katrin and Voelzke, Henry and Lagopoulos, Jim and Hatton, Sean N. and Hickie, Ian B. and Frey, Eva Maria and Carballedo, Angela and Brooks, Samantha J. and Vuletic, Daniella and Uhlmann, Anne and Veer, Ilya M. and Walter, Henrik and Schnell, Knut and Grotegerd, Dominik and Arolt, Volker and Kugel, Harald and Schramm, Elisabeth and Konrad, Carsten and Zurowski, Bartosz and Baune, Bernhard T. and van der Wee, Nic J. A. and van Tol, Marie-Jose and Penninx, Brenda W. J. H. and Thompson, Paul M. and Hibar, Derrek P. and Dannlowski, Udo and Grabe, Hans J.},
  title     = {Childhood adversity impacts on brain subcortical structures relevant to depression},
  series = {Journal of psychiatric research},
  volume    = {86},
  journal   = {Journal of psychiatric research},
  publisher = {Elsevier},
  address   = {Oxford},
  issn      = {0022-3956},
  doi       = {10.1016/j.jpsychires.2016.11.010},
  pages     = {58 -- 65},
  year      = {2017},
  abstract  = {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.},
  language  = {en}
}
@article{CreightonParsekianAngelopoulosetal.2018,
  author    = {Creighton, Andrea L. and Parsekian, Andrew D. and Angelopoulos, Michael and Jones, Benjamin M. and Bondurant, A. and Engram, M. and Lenz, Josefine and Overduin, Pier Paul and Grosse, Guido and Babcock, E. and Arp, Christopher D.},
  title     = {Transient Electromagnetic Surveys for the Determination of Talik Depth and Geometry Beneath Thermokarst Lakes},
  series = {Journal of geophysical research : Solid earth},
  volume    = {123},
  journal   = {Journal of geophysical research : Solid earth},
  number    = {11},
  publisher = {American Geophysical Union},
  address   = {Washington},
  issn      = {2169-9313},
  doi       = {10.1029/2018JB016121},
  pages     = {9310 -- 9323},
  year      = {2018},
  abstract  = {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.},
  language  = {en}
}
@misc{PatheNeuschaeferRubeNeuschaeferRubeHaasetal.2018,
  author    = {Pathe-Neusch{\"a}fer-Rube, Andrea and Neusch{\"a}fer-Rube, Frank and Haas, Gerald and Langoth-Fehringer, Nina and P{\"u}schel, Gerhard Paul},
  title     = {Cell-Based Reporter Release Assay to Determine the Potency of Proteolytic Bacterial Neurotoxins},
  series = {Toxins},
  journal   = {Toxins},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-418141},
  pages     = {10},
  year      = {2018},
  abstract  = {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.},
  language  = {en}
}
@article{HenkelNeuschaeferRubePatheNeuschaeferRubeetal.2009,
  author    = {Henkel, Janin and Neuschaefer-Rube, Frank and Pathe-Neuschaefer-Rube, Andrea and P{\"u}schel, Gerhard Paul},
  title     = {Aggravation by prostaglandin e-2 of interleukin-6-dependent insulin resistance in hepatocytes},
  issn      = {0270-9139},
  doi       = {10.1002/Hep.23064},
  year      = {2009},
  abstract  = {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.},
  language  = {en}
}
@article{PatheNeuschaeferRubeNeuschaeferRubeGenzetal.2015,
  author    = {Pathe-Neuschaefer-Rube, Andrea and Neuschaefer-Rube, Frank and Genz, Lara and P{\"u}schel, Gerhard Paul},
  title     = {Botulinum Neurotoxin Dose-Dependently Inhibits Release of Neurosecretory Vesicle-Targeted Luciferase from Neuronal Cells},
  series = {Alternatives to animal experimentation : ALTEX ; a journal for new paths in biomedical science},
  volume    = {32},
  journal   = {Alternatives to animal experimentation : ALTEX ; a journal for new paths in biomedical science},
  number    = {4},
  publisher = {Springer},
  address   = {Heidelberg},
  issn      = {1868-596X},
  pages     = {297 -- 306},
  year      = {2015},
  abstract  = {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.},
  language  = {en}
}
@article{PatheNeuschaeferRubeNeuschaeferRubeHaasetal.2018,
  author    = {Pathe-Neusch{\"a}fer-Rube, Andrea and Neusch{\"a}fer-Rube, Frank and Haas, Gerald and Langoth-Fehringer, Nina and P{\"u}schel, Gerhard Paul},
  title     = {Cell-Based Reporter Release Assay to Determine the Potency of Proteolytic Bacterial Neurotoxins},
  series = {Toxins},
  volume    = {10},
  journal   = {Toxins},
  number    = {9},
  publisher = {Molecular Diversity Preservation International (MDPI)},
  address   = {Basel},
  issn      = {2072-6651},
  doi       = {10.3390/toxins10090360},
  pages     = {1 -- 10},
  year      = {2018},
  abstract  = {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.},
  language  = {en}
}
@article{PatheNeuschaeferRubeNeuschaeferRubePueschel2005,
  author    = {Pathe-Neusch{\"a}fer-Rube, Andrea and Neusch{\"a}fer-Rube, Frank and P{\"u}schel, Gerhard Paul},
  title     = {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},
  year      = {2005},
  abstract  = {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.},
  language  = {en}
}
@article{NeuschaeferRubeHermosillaKunaetal.2005,
  author    = {Neusch{\"a}fer-Rube, Frank and Hermosilla, Ricardo and Kuna, Manuela and Pathe-Neusch{\"a}fer-Rube, Andrea and Schulein, R. and P{\"u}schel, Gerhard Paul},
  title     = {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},
  issn      = {0007-1188},
  year      = {2005},
  abstract  = {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},
  language  = {en}
}
@article{PatheNeuschaeferRubeNeuschaeferRubePueschel2004,
  author    = {Pathe-Neusch{\"a}fer-Rube, Andrea and Neusch{\"a}fer-Rube, Frank and P{\"u}schel, Gerhard Paul},
  title     = {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)},
  issn      = {0028-1298},
  year      = {2004},
  language  = {en}
}
@article{NeuschaeferRubeHermosillaKunaetal.2004,
  author    = {Neusch{\"a}fer-Rube, Frank and Hermosilla, Ricardo and Kuna, Manuela and Pathe-Neuschaefer-Rube, Andrea and P{\"u}schel, Gerhard Paul},
  title     = {Agonist-induced desensitization of rat prostaglandin EP3 receptor isoforms},
  issn      = {0028-1298},
  year      = {2004},
  language  = {en}
}
@article{NeuschaeferRubeLieskeKunaetal.2014,
  author    = {Neuschaefer-Rube, Frank and Lieske, Stefanie and Kuna, Manuela and Henkel, Janin and Perry, Rachel J. and Erion, Derek M. and Pesta, Dominik and Willmes, Diana M. and Brachs, Sebastian and von Loeffelholz, Christian and Tolkachov, Alexander and Schupp, Michael and Pathe-Neuschaefer-Rube, Andrea and Pfeiffer, Andreas F. H. and Shulman, Gerald I. and P{\"u}schel, Gerhard Paul and Birkenfeld, Andreas L.},
  title     = {The mammalian INDY homolog is induced by CREB in a rat model of type 2 diabetes},
  series = {Diabetes : a journal of the American Diabetes Association},
  volume    = {63},
  journal   = {Diabetes : a journal of the American Diabetes Association},
  number    = {3},
  publisher = {American Diabetes Association},
  address   = {Alexandria},
  issn      = {0012-1797},
  pages     = {1048 -- 1057},
  year      = {2014},
  language  = {en}
}
@article{NeuschaeferRubePatheNeuschaeferRubePueschel2022,
  author    = {Neusch{\"a}fer-Rube, Frank and Pathe-Neusch{\"a}fer-Rube, Andrea and P{\"u}schel, Gerhard Paul},
  title     = {Discrimination of the activity of low-affinity wild-type and high-affinity mutant recombinant BoNT/B by a SIMA cell-based reporter release assay},
  series = {Toxins},
  volume    = {14},
  journal   = {Toxins},
  edition   = {1},
  publisher = {MDPI},
  address   = {Basel, Schweiz},
  issn      = {2072-6651},
  doi       = {10.3390/toxins14010065},
  pages     = {1 -- 11},
  year      = {2022},
  abstract  = {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.},
  language  = {en}
}
@article{NeuschaeferRubePatheNeuschaeferRubeHippenstieletal.2018,
  author    = {Neusch{\"a}fer-Rube, Frank and Pathe-Neusch{\"a}fer-Rube, Andrea and Hippenstiel, Stefan and P{\"u}schel, Gerhard Paul},
  title     = {PGE(2) enhanced TNF alpha-mediated IL-8 induction in monocytic cell lines and PBMC},
  series = {Cytokine},
  volume    = {113},
  journal   = {Cytokine},
  publisher = {Elsevier},
  address   = {London},
  issn      = {1043-4666},
  doi       = {10.1016/j.cyto.2018.06.020},
  pages     = {105 -- 116},
  year      = {2018},
  abstract  = {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.},
  language  = {en}
}
@article{PatheNeuschaeferRubeNeuschaeferRubePueschel2021,
  author    = {Pathe-Neusch{\"a}fer-Rube, Andrea and Neusch{\"a}fer-Rube, Frank and P{\"u}schel, Gerhard Paul},
  title     = {Cell-based reporter release assay to determine the activity of calcium-dependent neurotoxins and neuroactive pharmaceuticals},
  series = {Toxins / Molecular Diversity Preservation International (MDPI)},
  volume    = {13},
  journal   = {Toxins / Molecular Diversity Preservation International (MDPI)},
  number    = {4},
  publisher = {MDPI},
  address   = {Basel},
  issn      = {2072-6651},
  doi       = {10.3390/toxins13040247},
  pages     = {13},
  year      = {2021},
  abstract  = {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.},
  language  = {en}
}
@misc{PatheNeuschaeferRubeNeuschaeferRubePueschel2021,
  author    = {Pathe-Neusch{\"a}fer-Rube, Andrea and Neusch{\"a}fer-Rube, Frank and P{\"u}schel, Gerhard Paul},
  title     = {Cell-based reporter release assay to determine the activity of calcium-dependent neurotoxins and neuroactive pharmaceuticals},
  series = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
  journal   = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
  number    = {1139},
  issn      = {1866-8372},
  doi       = {10.25932/publishup-50322},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-503225},
  pages     = {15},
  year      = {2021},
  abstract  = {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.},
  language  = {en}
}
@misc{NeuschaeferRubePatheNeuschaeferRubePueschel2022,
  author    = {Neusch{\"a}fer-Rube, Frank and Pathe-Neusch{\"a}fer-Rube, Andrea and P{\"u}schel, Gerhard Paul},
  title     = {Discrimination of the Activity of Low-Affinity Wild-Type and High-Affinity Mutant Recombinant BoNT/B by a SIMA Cell-Based Reporter Release Assay},
  series = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
  journal   = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
  publisher = {Universit{\"a}tsverlag Potsdam},
  address   = {Potsdam},
  issn      = {1866-8372},
  doi       = {10.25932/publishup-55803},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-558032},
  pages     = {1 -- 11},
  year      = {2022},
  abstract  = {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.},
  language  = {en}
}
@article{RenteriaSchmaalHibaretal.2017,
  author    = {Renteria, Miguel E. and Schmaal, L. and Hibar, D. P. and Couvy-Duchesne, B. and Strike, L. T. and Mills, N. T. and de Zubicaray, Greig. I. and McMahon, Katie. L. and Medland, Sarah E. and Gillespie, N. A. and Hatton, S. N. and Lagopoulos, J. and Veltman, D. J. and van der Wee, N. and van Erp, T. G. M. and Wittfeld, K. and Grabe, H. J. and Block, Andrea and Hegenscheid, K. and Voelzke, H. and Veer, I. M. and Walter, H. and Schnell, K. and Schramm, E. and Normann, C. and Schoepf, Dieter and Konrad, C. and Zurowski, B. and Godlewska, B. R. and Cowen, P. J. and Penninx, B. W. J. H. and Jahanshad, N. and Thompson, Paul M. and Wright, M. J. and Martin, N. G. and Christensen, H. and Hickie, I. B.},
  title     = {Subcortical brain structure and suicidal behaviour in major depressive disorder: a meta-analysis from the ENIGMA-MDD working group},
  series = {Translational Psychiatry},
  volume    = {7},
  journal   = {Translational Psychiatry},
  publisher = {Nature Publ. Group},
  address   = {New York},
  organization    = {ENIGMA-Major Depressive Disorde},
  issn      = {2158-3188},
  doi       = {10.1038/tp.2017.84},
  pages     = {2301 -- 2320},
  year      = {2017},
  language  = {en}
}
@article{WeberAbuAyyashAbueladasetal.2009,
  author    = {Weber, Michael H. and Abu-Ayyash, Khalil and Abueladas, Abdel-Rahman and Agnon, Amotz and Alasonati-Taš{\´a}rov{\´a}, Zuzana and Al-Zubi, Hashim and Babeyko, Andrey and Bartov, Yuval and Bauer, Klaus and Becken, Michael and Bedrosian, Paul A. and Ben-Avraham, Zvi and Bock, G{\"u}nter and Bohnhoff, Marco and Bribach, Jens and Dulski, Peter and Ebbing, Joerg and El-Kelani, Radwan J. and Foerster, Andrea and F{\"o}rster, Hans-J{\"u}rgen and Frieslander, Uri and Garfunkel, Zvi and G{\"o}tze, Hans-J{\"u}rgen and Haak, Volker and Haberland, Christian and Hassouneh, Mohammed and Helwig, Stefan L. and Hofstetter, Alfons and Hoffmann-Rothe, Arne and Jaeckel, Karl-Heinz and Janssen, Christoph and Jaser, Darweesh and Kesten, Dagmar and Khatib, Mohammed Ghiath and Kind, Rainer and Koch, Olaf and Koulakov, Ivan and Laske, Maria Gabi and Maercklin, Nils},
  title     = {Anatomy of the Dead Sea transform from lithospheric to microscopic scale},
  issn      = {8755-1209},
  doi       = {10.1029/2008rg000264},
  year      = {2009},
  abstract  = {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.},
  language  = {en}
}
@article{KhudairMarcuzziNgetal.2022,
  author    = {Khudair, Mohammed and Marcuzzi, Anna and Ng, Kwok and Tempest, Gavin Daniel and Bartoš, František and Peric, Ratko and Maier, Maximilian and Beccia, Flavia and Boccia, Stefania and Brandes, Mirko and Cardon, Greet and Carlin, Angela and Castagna, Carolina and Chaabene, Helmi and Chalkley, Anna and Ciaccioni, Simone and Cieślińska-Świder, Joanna and Čingienė, Vilma and Cortis, Cristina and Corvino, Chiara and de Geus, Eco J. C. and Di Baldassarre, Angela and Di Credico, Andrea and Drid, Patrik and Tarazaga, Rosa Ma Fern{\´a}ndez and Gall{\`e}, Francesca and S{\´a}nchez, Esther Garcia and Gebremariam, Mekdes and Ghinassi, Barbara and Goudas, Marios and Hayes, Grainne and Honorio, Samuel and Izzicupo, Pascal and Jahre, Henriette and Jelsma, Judith and Juric, Petra and Kolovelonis, Athanasios and Kongsvold, Atle and Kouidi, Evangelia and Mansergh, Fiona and Masanovic, Bojan and Mekonnen, Teferi and Mork, Paul Jarle and Murphy, Marie and O'Hara, Kelly and Torun, Ayse Ozbil and Palumbo, Federico and Popovic, Stevo and Prieske, Olaf and Puharic, Zrinka and Ribeiro, Jos{\´e} Carlos and Rumbold, Penny Louise Sheena and Sandu, Petru and Soric, Maroje and Stavnsbo, Mette and Syrmpas, Ioannis and van der Ploeg, Hidde P. and Van Hoye, Aur{\´e}lie and Vilela, Sofia and Woods, Catherine and Wunsch, Kathrin and Caprinica, Laura and MacDonncha, Ciaran and Ling, Fiona Chun Man},
  title     = {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},
  series = {BMJ open},
  volume    = {12},
  journal   = {BMJ open},
  number    = {9},
  publisher = {BMJ Publishing Group},
  address   = {London},
  organization    = {DE-PASS},
  issn      = {2044-6055},
  doi       = {10.1136/bmjopen-2021-059202},
  pages     = {8},
  year      = {2022},
  abstract  = {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.},
  language  = {en}
}
@article{DierckeKuckeinCauleyetal.2022,
  author    = {Diercke, Andrea and Kuckein, Christoph and Cauley, Paul Wilson and Poppenh{\"a}ger, Katja and Alvarado-G{\´o}mez, Juli{\´a}n David and Dineva, Ekaterina Ivanova and Denker, Carsten},
  title     = {Solar H alpha excess during Solar Cycle 24 from full-disk filtergrams of the Chromospheric Telescope},
  series = {Astronomy and astrophysics : an international weekly journal},
  volume    = {661},
  journal   = {Astronomy and astrophysics : an international weekly journal},
  publisher = {EDP Sciences},
  address   = {Les Ulis},
  issn      = {1432-0746},
  doi       = {10.1051/0004-6361/202040091},
  pages     = {14},
  year      = {2022},
  abstract  = {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.},
  language  = {en}
}
@book{KubanRottaNolteetal.2023,
  author    = {Kuban, Robert and Rotta, Randolf and Nolte, J{\"o}rg and Chromik, Jonas and Beilharz, Jossekin Jakob and Pirl, Lukas and Friedrich, Tobias and Lenzner, Pascal and Weyand, Christopher and Juiz, Carlos and Bermejo, Belen and Sauer, Joao and Coelh, Leandro dos Santos and Najafi, Pejman and P{\"u}nter, Wenzel and Cheng, Feng and Meinel, Christoph and Sidorova, Julia and Lundberg, Lars and Vogel, Thomas and Tran, Chinh and Moser, Irene and Grunske, Lars and Elsaid, Mohamed Esameldin Mohamed and Abbas, Hazem M. and Rula, Anisa and Sejdiu, Gezim and Maurino, Andrea and Schmidt, Christopher and H{\"u}gle, Johannes and Uflacker, Matthias and Nozza, Debora and Messina, Enza and Hoorn, Andr{\´e} van and Frank, Markus and Schulz, Henning and Alhosseini Almodarresi Yasin, Seyed Ali and Nowicki, Marek and Muite, Benson K. and Boysan, Mehmet Can and Bianchi, Federico and Cremaschi, Marco and Moussa, Rim and Abdel-Karim, Benjamin M. and Pfeuffer, Nicolas and Hinz, Oliver and Plauth, Max and Polze, Andreas and Huo, Da and Melo, Gerard de and Mendes Soares, F{\´a}bio and Oliveira, Roberto C{\´e}lio Lim{\~a}o de and Benson, Lawrence and Paul, Fabian and Werling, Christian and Windheuser, Fabian and Stojanovic, Dragan and Djordjevic, Igor and Stojanovic, Natalija and Stojnev Ilic, Aleksandra and Weidmann, Vera and Lowitzki, Leon and Wagner, Markus and Ifa, Abdessatar Ben and Arlos, Patrik and Megia, Ana and Vendrell, Joan and Pfitzner, Bjarne and Redondo, Alberto and R{\´i}os Insua, David and Albert, Justin Amadeus and Zhou, Lin and Arnrich, Bert and Szab{\´o}, Ildik{\´o} and Fodor, Szabina and Ternai, Katalin and Bhowmik, Rajarshi and Campero Durand, Gabriel and Shevchenko, Pavlo and Malysheva, Milena and Prymak, Ivan and Saake, Gunter},
  title     = {HPI Future SOC Lab - Proceedings 2019},
  number    = {158},
  editor    = {Meinel, Christoph and Polze, Andreas and Beins, Karsten and Strotmann, Rolf and Seibold, Ulrich and R{\"o}dszus, Kurt and M{\"u}ller, J{\"u}rgen},
  publisher = {Universit{\"a}tsverlag Potsdam},
  address   = {Potsdam},
  isbn      = {978-3-86956-564-4},
  issn      = {1613-5652},
  doi       = {10.25932/publishup-59791},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-597915},
  publisher      = {Universit{\"a}t Potsdam},
  pages     = {xi, 301},
  year      = {2023},
  abstract  = {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.},
  language  = {en}
}
@article{LeunertEckertPauletal.2014,
  author    = {Leunert, Franziska and Eckert, Werner and Paul, Andrea and Gerhardt, Volkmar and Grossart, Hans-Peter},
  title     = {Phytoplankton response to UV-generated hydrogen peroxide from natural organic matter},
  series = {Journal of plankton research},
  volume    = {36},
  journal   = {Journal of plankton research},
  number    = {1},
  publisher = {Oxford Univ. Press},
  address   = {Oxford},
  issn      = {0142-7873},
  doi       = {10.1093/plankt/fbt096},
  pages     = {185 -- 197},
  year      = {2014},
  abstract  = {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.},
  language  = {en}
}