@article{HammesAndreassenSpoelgenetal.2005, author = {Hammes, Annette and Andreassen, Thomas K. and Spoelgen, Robert and Raila, Jens and Hubner, Norbert and Schulz, Herbert and Metzger, Jochen and Schweigert, Florian J. and Luppa, Peter B. and Nykjaer, Andreas and Willnow, Thomas E.}, title = {Role of endocytosis in cellular uptake of sex steroids}, issn = {0092-8674}, year = {2005}, abstract = {Androgens and estrogens are transported bound to the sex hormone binding globulin (SHBG). SHBG is believed to keep sex steroids inactive and to control the amount of free hormones that enter cells by passive diffusion. Contrary to the free hormone hypothesis, we demonstrate that megalin, an endocytic receptor in reproductive tissues, acts as a pathway for cellular uptake of biologically active androgens and estrogens bound to SHBG. In line with this function, lack of receptor expression in megalin knockout mice results in impaired descent of the testes into the scrotum in males and blockade of vagina opening in females. Both processes are critically dependent on sex-steroid signaling, and similar defects are seen in animals treated with androgen- or estrogen-receptor antagonists. Thus, our findings uncover the existence of endocytic pathways for protein bound androgens and estrogens and their crucial role in development of the reproductive organs}, language = {en} } @article{FlorianLopezLuqueOspinaAlvarezetal.2016, author = {Florian, Norbert and Lopez-Luque, Raquel and Ospina-Alvarez, Natalia and Hufnagel, Levente and Green, Andy J.}, title = {Influence of a carp invasion on the zooplankton community in Laguna Medina, a Mediterranean shallow lake}, series = {Limnetica}, volume = {35}, journal = {Limnetica}, publisher = {Asociaci{\~A}³n Espan{\~A}µla de Limnolog{\~A}­a}, address = {Mislata (Valencia)}, issn = {0213-8409}, pages = {397 -- 411}, year = {2016}, abstract = {The common carp (Cyprinus carpio) is a highly invasive species and an ecological engineer. It has been repeatedly shown to increase nutrient concentrations and phytoplankton biomass while destroying submerged macrophytes, although there are few studies from the Mediterranean region. We studied its impact on the zooplankton community in Laguna de Medina lake, a shallow lake in Jerez de la Frontera, south-west Spain. Carp were removed with rotenone in 2007 but returned in 2010-2011. We compared zooplankton sampled monthly from 8 points from May to December in 2008 (without carp) and 2012 (with carp). Extensive macrophyte beds present in 2008 were absent in 2012. As expected, chlorophyll-a concentrations, turbidity, total suspended solids and total phosphorus were much higher in 2012. Zooplankton richness decreased from 21 taxa in 2008 to 8 taxa in 2012, accompanied by a decrease in Shannon-Wiener diversity, an increase in Evenness and a change in size distribution with loss of larger taxa. In 2008, the crustaceans were dominated by the macrocladocerans Daphnia magna and Moina brachiata and the large calanoid copepod Arctodiaptomus salinus. In 2012, these three taxa were completely absent and the zooplankton was dominated by the alien cyclopoid Acanthocyclops americanus and the rotifers Brachionus plicatilis and Keratella quadrata. Our results confirm the disappearance of macrocladocera reported by others in mesocosm experiments with carp, and suggest that alien carp facilitate the spread of the alien copepod A. americanus.}, language = {en} } @article{SchlagOsterzielOezceliketal.2008, author = {Schlag, Peter M. and Osterziel, Karl Joseph and {\"O}zcelik, Cemil and Scherneck, Siegfried and Wenzel, Katrin and Daskalow, Katjana and Herse, Florian and Seitz, Susanne and Zacharias, Ute and Schenk, J{\"o}rg A. and Schulz, Herbert and H{\"u}bner, Norbert and Micheel, Burkhard}, title = {The protein phosphatase 1 inhibitor KEPI is down regulated in breast cancer cell lines and tissues and involved in the regulation of the tumour suppressor EGR1 via the MEK-ERK pathway}, year = {2008}, abstract = {KEPI is a protein kinase C-potentiated inhibitory protein for type 1 Ser/Thr protein phosphatases. We found no or reduced expression of KEPI in breast cancer cell lines, breast tumors and metastases in comparison to normal breast cell lines and tissues, respectively. KEPI protein expression and ubiquitous localization was detected with a newly generated antibody. Ectopic KEPI expression in MCF7 breast cancer cells induced differential expression of 95 genes, including the up-regulation of the tumor suppressors EGR1 (early growth response 1) and PTEN (phosphatase and tensin homolog), which is regulated by EGR1. We further show that the up-regulation of EGR1 in MCF7/KEPI cells is mediated by MEK-ERK signaling. The inhibition of this pathway by the MEK inhibitor UO126 led to a strong decrease in EGR1 expression in MCF7/KEPI cells. These results reveal a novel role for KEPI in the regulation of the tumor suppressor gene EGR1 via activation of the MEK-ERK MAPK pathway.}, language = {en} } @inproceedings{PoppBlaumDomptailetal.2006, author = {Popp, Alexander and Blaum, Niels and Domptail, Stephanie and Herpel, Nicole and Gr{\"o}ngr{\"o}ft, Alexander and Hoffman, T. T. and J{\"u}rgens, Norbert and Milton, Sue and Nuppenau, Ernst-August and Rossmanith, Eva and Schmidt, Michael and Vogel, Melanie and Vohland, Katrin and Jeltsch, Florian}, title = {From satellite imagery to soil-plant interactions}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-7302}, year = {2006}, abstract = {Decisions for the conservation of biodiversity and sustainable management of natural resources are typically related to large scales, i.e. the landscape level. However, understanding and predicting the effects of land use and climate change on scales relevant for decision-making requires to include both, large scale vegetation dynamics and small scale processes, such as soil-plant interactions. Integrating the results of multiple BIOTA subprojects enabled us to include necessary data of soil science, botany, socio-economics and remote sensing into a high resolution, process-based and spatially-explicit model. Using an example from a sustainably-used research farm and a communally used and degraded farming area in semiarid southern Namibia we show the power of simulation models as a tool to integrate processes across disciplines and scales.}, language = {en} } @article{GarbusowSchadSommeretal.2014, author = {Garbusow, Maria and Schad, Daniel and Sommer, Christian and Juenger, Elisabeth and Sebold, Miriam and Friedel, Eva and Wendt, Jean and Kathmann, Norbert and Schlagenhauf, Florian and Zimmermann, Ulrich S. and Heinz, Andreas and Huys, Quentin J. M. and Rapp, Michael A.}, title = {Pavlovian-to-instrumental transfer in alcohol dependence: a pilot study}, series = {Neuropsychobiology : international journal of experimental and clinical research in biological psychiatry, pharmacopsychiatry, Biological Psychology/Pharmacopsychology and Pharmacoelectroencephalography}, volume = {70}, journal = {Neuropsychobiology : international journal of experimental and clinical research in biological psychiatry, pharmacopsychiatry, Biological Psychology/Pharmacopsychology and Pharmacoelectroencephalography}, number = {2}, publisher = {Karger}, address = {Basel}, issn = {0302-282X}, doi = {10.1159/000363507}, pages = {111 -- 121}, year = {2014}, abstract = {Background: Pavlovian processes are thought to play an important role in the development, maintenance and relapse of alcohol dependence, possibly by influencing and usurping ongoing thought and behavior. The influence of pavlovian stimuli on ongoing behavior is paradigmatically measured by pavlovian-to-instrumental transfer (PIT) tasks. These involve multiple stages and are complex. Whether increased PIT is involved in human alcohol dependence is uncertain. We therefore aimed to establish and validate a modified PIT paradigm that would be robust, consistent and tolerated by healthy controls as well as by patients suffering from alcohol dependence, and to explore whether alcohol dependence is associated with enhanced PIT. Methods: Thirty-two recently detoxified alcohol-dependent patients and 32 age- and gender-matched healthy controls performed a PIT task with instrumental go/no-go approach behaviors. The task involved both pavlovian stimuli associated with monetary rewards and losses, and images of drinks. Results: Both patients and healthy controls showed a robust and temporally stable PIT effect. Strengths of PIT effects to drug-related and monetary conditioned stimuli were highly correlated. Patients more frequently showed a PIT effect, and the effect was stronger in response to aversively conditioned CSs (conditioned suppression), but there was no group difference in response to appetitive CSs. Conclusion: The implementation of PIT has favorably robust properties in chronic alcohol-dependent patients and in healthy controls. It shows internal consistency between monetary and drug-related cues. The findings support an association of alcohol dependence with an increased propensity towards PIT.}, language = {en} } @article{SeboldDesernoNebeetal.2014, author = {Sebold, Miriam and Deserno, Lorenz and Nebe, Stefan and Schad, Daniel and Garbusow, Maria and Haegele, Claudia and Keller, Juergen and Juenger, Elisabeth and Kathmann, Norbert and Smolka, Michael N. and Rapp, Michael A. and Schlagenhauf, Florian and Heinz, Andreas and Huys, Quentin J. M.}, title = {Model-based and model-free decisions in alcohol dependence}, series = {Neuropsychobiology : international journal of experimental and clinical research in biological psychiatry, pharmacopsychiatry, Biological Psychology/Pharmacopsychology and Pharmacoelectroencephalography}, volume = {70}, journal = {Neuropsychobiology : international journal of experimental and clinical research in biological psychiatry, pharmacopsychiatry, Biological Psychology/Pharmacopsychology and Pharmacoelectroencephalography}, number = {2}, publisher = {Karger}, address = {Basel}, issn = {0302-282X}, doi = {10.1159/000362840}, pages = {122 -- 131}, year = {2014}, abstract = {Background: Human and animal work suggests a shift from goal-directed to habitual decision-making in addiction. However, the evidence for this in human alcohol dependence is as yet inconclusive. Methods: Twenty-six healthy controls and 26 recently detoxified alcohol-dependent patients underwent behavioral testing with a 2-step task designed to disentangle goal-directed and habitual response patterns. Results: Alcohol-dependent patients showed less evidence of goal-directed choices than healthy controls, particularly after losses. There was no difference in the strength of the habitual component. The group differences did not survive controlling for performance on the Digit Symbol Substitution Task. Conclusion: Chronic alcohol use appears to selectively impair goal-directed function, rather than promoting habitual responding. It appears to do so particularly after nonrewards, and this may be mediated by the effects of alcohol on more general cognitive functions subserved by the prefrontal cortex.}, language = {en} } @article{GarbusowSchadSeboldetal.2016, author = {Garbusow, Maria and Schad, Daniel and Sebold, Miriam and Friedel, Eva and Bernhardt, Nadine and Koch, Stefan P. and Steinacher, Bruno and Kathmann, Norbert and Geurts, Dirk E. M. and Sommer, Christian and Mueller, Dirk K. and Nebe, Stephan and Paul, Soeren and Wittchen, Hans-Ulrich and Zimmermann, Ulrich S. and Walter, Henrik and Smolka, Michael N. and Sterzer, Philipp and Rapp, Michael A. and Huys, Quentin J. M. and Schlagenhauf, Florian and Heinz, Andreas}, title = {Pavlovian-to-instrumental transfer effects in the nucleus accumbens relate to relapse in alcohol dependence}, series = {Addiction biology}, volume = {21}, journal = {Addiction biology}, publisher = {Wiley-Blackwell}, address = {Hoboken}, issn = {1355-6215}, doi = {10.1111/adb.12243}, pages = {719 -- 731}, year = {2016}, abstract = {In detoxified alcohol-dependent patients, alcohol-related stimuli can promote relapse. However, to date, the mechanisms by which contextual stimuli promote relapse have not been elucidated in detail. One hypothesis is that such contextual stimuli directly stimulate the motivation to drink via associated brain regions like the ventral striatum and thus promote alcohol seeking, intake and relapse. Pavlovian-to-Instrumental-Transfer (PIT) may be one of those behavioral phenomena contributing to relapse, capturing how Pavlovian conditioned (contextual) cues determine instrumental behavior (e.g. alcohol seeking and intake). We used a PIT paradigm during functional magnetic resonance imaging to examine the effects of classically conditioned Pavlovian stimuli on instrumental choices in n=31 detoxified patients diagnosed with alcohol dependence and n=24 healthy controls matched for age and gender. Patients were followed up over a period of 3 months. We observed that (1) there was a significant behavioral PIT effect for all participants, which was significantly more pronounced in alcohol-dependent patients; (2) PIT was significantly associated with blood oxygen level-dependent (BOLD) signals in the nucleus accumbens (NAcc) in subsequent relapsers only; and (3) PIT-related NAcc activation was associated with, and predictive of, critical outcomes (amount of alcohol intake and relapse during a 3 months follow-up period) in alcohol-dependent patients. These observations show for the first time that PIT-related BOLD signals, as a measure of the influence of Pavlovian cues on instrumental behavior, predict alcohol intake and relapse in alcohol dependence.}, language = {en} }