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Sebold, Miriam ; Nebe, Stephan ; Garbusow, Maria ; Guggenmos, Matthias ; Schad, Daniel ; Beck, Anne ; Kuitunen-Paul, Sören ; Sommer, Christian ; Frank, Robin ; Neu, Peter ; Zimmermann, Ulrich S. ; Rapp, Michael A. ; Smolka, Michael N. ; Huys, Quentin J. M. ; Schlagenhauf, Florian ; Heinz, Andreas
BACKGROUND: Addiction is supposedly characterized by a shift from goal-directed to habitual decision making, thus facilitating automatic drug intake. The two-step task allows distinguishing between these mechanisms by computationally modeling goal-directed and habitual behavior as model-based and model-free control. In addicted patients, decision making may also strongly depend upon drug-associated expectations. Therefore, we investigated model-based versus model-free decision making and its neural correlates as well as alcohol expectancies in alcohol-dependent patients and healthy controls and assessed treatment outcome in patients. METHODS: Ninety detoxified, medication-free, alcohol-dependent patients and 96 age-and gender-matched control subjects underwent functional magnetic resonance imaging during the two-step task. Alcohol expectancies were measured with the Alcohol Expectancy Questionnaire. Over a follow-up period of 48 weeks, 37 patients remained abstinent and 53 patients relapsed as indicated by the Alcohol Timeline Followback method. RESULTS: Patients who relapsed displayed reduced medial prefrontal cortex activation during model-based decision making. Furthermore, high alcohol expectancies were associated with low model-based control in relapsers, while the opposite was observed in abstainers and healthy control subjects. However, reduced model-based control per se was not associated with subsequent relapse. CONCLUSIONS: These findings suggest that poor treatment outcome in alcohol dependence does not simply result from a shift from model-based to model-free control but is instead dependent on the interaction between high drug expectancies and low model-based decision making. Reduced model-based medial prefrontal cortex signatures in those who relapse point to a neural correlate of relapse risk. These observations suggest that therapeutic interventions should target subjective alcohol expectancies.
Trauth, Martin H. ; Bergner, Andreas G. N. ; Foerster, Verena ; Junginger, Annett ; Maslin, Mark A. ; Schäbitz, Frank
Episodes of environmental stability and instability may be equally important for African hominin speciation, dispersal, and cultural innovation. Three examples of a change from stable to unstable environmental conditions are presented on three different time scales: (1) the Mid Holocene (MH) wet dry transition in the Chew Bahir basin (Southern Ethiopian Rift; between 11 ka and 4 ka), (2) the MIS 5-4 transition in the Naivasha basin (Central Kenya Rift; between 160 ka and 50 ka), and (3) the Early Mid Pleistocene Transition (EMPT) in the Olorgesailie basin (Southern Kenya Rift; between 1.25 Ma and 0.4 Ma). A probabilistic age modeling technique is used to determine the timing of these transitions, taking into account possible abrupt changes in the sedimentation rate including episodes of no deposition (hiatuses). Interestingly, the stable-unstable conditions identified in the three records are always associated with an orbitally-induced decrease of insolation: the descending portion of the 800 kyr cycle during the EMPT, declining eccentricity after the 115 ka maximum at the MIS 5-4 transition, and after similar to 10 ka. This observation contributes to an evidence-based discussion of the possible mechanisms causing the switching between environmental stability and instability in Eastern Africa at three different orbital time scales (10,000 to 1,000,000 years) during the Cenozoic. This in turn may lead to great insights into the environmental changes occurring at the same time as hominin speciation, brain expansion, dispersal out of Africa, and cultural innovations and may provide key evidence to build new hypotheses regarding the causes of early human evolution. (C) 2015 Elsevier Ltd. All rights reserved.
Szymanski, Kolja V. ; Tönnies, Mario ; Becher, Anne ; Fatykhova, Diana ; N'Guessan, Philippe D. ; Gutbier, Birgitt ; Klauschen, Frederick ; Neuschäfer-Rube, Frank ; Schneider, Paul ; Rückert, Jens ; Neudecker, Jens ; Bauer, Torsten T. ; Dalhoff, Klaus ; Droemann, Daniel ; Gruber, Achim D. ; Kershaw, Olivia ; Temmesfeld-Wollbrueck, Bettina ; Suttorp, Norbert ; Hippenstiel, Stefan ; Hocke, Andreas C.
The majority of cases of community-acquired pneumonia are caused by Streptococcus pneumoniae and most studies on pneumococcal host interaction are based on cell culture or animal experiments. Thus, little is known about infections in human lung tissue.
Cyclooxygenase-2 and its metabolites play an important regulatory role in lung inflammation. Therefore, we established a pneumococcal infection model on human lung tissue demonstrating mitogen-activated protein kinase (MAPK)-dependent induction of cyclooxygenase-2 and its related metabolites.
In addition to alveolar macrophages and the vascular endothelium, cyclooxygenase-2 was upregulated in alveolar type II but not type I epithelial cells, which was confirmed in lungs of patients suffering from acute pneumonia. Moreover, we demonstrated the expression profile of all four E prostanoid receptors at the mRNA level and showed functionality of the E prostanoid(4) receptor by cyclic adenosine monophosphate production. Additionally, in comparison to previous studies, cyclooxygenase-2/prostaglandin E-2 related pro- and anti-inflammatory mediator regulation was partly confirmed in human lung tissue after pneumococcal infection.
Overall, cell type-specific and MAPK-dependent cyclooxygenase-2 expression and prostaglandin E-2 formation in human lung tissue may play an important role in the early phase of pneumococcal infections.