@article{SalmanHaiderSchreinerKendletal.2019,
  author    = {Salman Haider, Malik and Schreiner, Jochen and Kendl, Sabine and Kroiss, Matthias and Luxenhofer, Robert},
  title     = {A Micellar Mitotane Formulation with High Drug-Loading and Solubility: Physico-Chemical Characterization and Cytotoxicity Studies in 2D and 3D In Vitro Tumor Models},
  series = {Macromolecular Bioscience},
  volume    = {20},
  journal   = {Macromolecular Bioscience},
  number    = {1},
  doi       = {10.1002/mabi.201900178},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-206224},
  pages     = {1900178},
  year      = {2019},
  abstract  = {Adrenocortical carcinoma (ACC) is a rare tumor and prognosis is overall poor but heterogeneous. Mitotane (MT) has been used for treatment of ACC for decades, either alone or in combination with cytotoxic chemotherapy. Even at doses up to 6 g per day, more than half of the patients do not achieve targeted plasma concentration (14-20 mg L\(^{-1}\)) even after many months of treatment due to low water solubility, bioavailability, and unfavorable pharmacokinetic profile. Here a novel MT nanoformulation with very high MT concentrations in physiological aqueous media is reported. The MT-loaded nanoformulations are characterized by Fourier transform infrared spectroscopy, differential scanning calorimetry, and powder X-ray diffraction which confirms the amorphous nature of the drug. The polymer itself does not show any cytotoxicity in adrenal and liver cell lines. By using the ACC model cell line NCI-H295 both in monolayers and tumor cell spheroids, micellar MT is demonstrated to exhibit comparable efficacy to its ethanol solution. It is postulated that this formulation will be suitable for i.v. application and rapid attainment of therapeutic plasma concentrations. In conclusion, the micellar formulation is considered a promising tool to alleviate major drawbacks of current MT treatment while retaining bioactivity toward ACC in vitro.},
  language  = {en}
}
@article{GonzalezDornerBretzetal.2019,
  author    = {Gonz{\´a}lez, Mar{\´i}a Magdalena and Dorner, Daniela and Bretz, Thomas and Garc{\´i}a-Gonz{\´a}lez, Jos{\´e} Andr{\´e}s},
  title     = {Unbiased long-term monitoring at TeV energies},
  series = {Galaxies},
  volume    = {7},
  journal   = {Galaxies},
  number    = {2},
  issn      = {2075-4434},
  doi       = {10.3390/galaxies7020051},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-197389},
  year      = {2019},
  abstract  = {For the understanding of the variable, transient and non-thermal universe, unbiased long-term monitoring is crucial. To constrain the emission mechanisms at the highest energies, it is important to characterize the very high energy emission and its correlation with observations at other wavelengths. At very high energies, only a limited number of instruments is available. This article reviews the current status of monitoring of the extra-galactic sky at TeV energies.},
  language  = {en}
}
@article{WaiderPoppMlinaretal.2019,
  author    = {Waider, Jonas and Popp, Sandy and Mlinar, Boris and Montalbano, Alberto and Bonfiglio, Francesco and Aboagye, Benjamin and Thuy, Elisabeth and Kern, Raphael and Thiel, Christopher and Araragi, Naozumi and Svirin, Evgeniy and Schmitt-B{\"o}hrer, Angelika G. and Corradetti, Renato and Lowry, Christopher A. and Lesch, Klaus-Peter},
  title     = {Serotonin deficiency increases context-dependent fear learning through modulation of hippocampal activity},
  series = {Frontiers in Neuroscience},
  volume    = {13},
  journal   = {Frontiers in Neuroscience},
  number    = {245},
  issn      = {1662-453X},
  doi       = {10.3389/fnins.2019.00245},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-196077},
  year      = {2019},
  abstract  = {Brain serotonin (5-hydroxytryptamine, 5-HT) system dysfunction is implicated in exaggerated fear responses triggering various anxiety-, stress-, and trauma-related disorders. However, the underlying mechanisms are not well understood. Here, we investigated the impact of constitutively inactivated 5-HT synthesis on context-dependent fear learning and extinction using tryptophan hydroxylase 2 (Tph2) knockout mice. Fear conditioning and context-dependent fear memory extinction paradigms were combined with c-Fos imaging and electrophysiological recordings in the dorsal hippocampus (dHip). Tph2 mutant mice, completely devoid of 5-HT synthesis in brain, displayed accelerated fear memory formation and increased locomotor responses to foot shock. Furthermore, recall of context-dependent fear memory was increased. The behavioral responses were associated with increased c-Fos expression in the dHip and resistance to foot shock-induced impairment of hippocampal long-term potentiation (LTP). In conclusion, increased context-dependent fear memory resulting from brain 5-HT deficiency involves dysfunction of the hippocampal circuitry controlling contextual representation of fear-related behavioral responses.},
  language  = {en}
}
@article{BreitenbachLorenzDandekar2019,
  author    = {Breitenbach, Tim and Lorenz, Kristina and Dandekar, Thomas},
  title     = {How to steer and control ERK and the ERK signaling cascade exemplified by looking at cardiac insufficiency},
  series = {International Journal of Molecular Sciences},
  volume    = {20},
  journal   = {International Journal of Molecular Sciences},
  number    = {9},
  issn      = {1422-0067},
  doi       = {10.3390/ijms20092179},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-285164},
  year      = {2019},
  abstract  = {Mathematical optimization framework allows the identification of certain nodes within a signaling network. In this work, we analyzed the complex extracellular-signal-regulated kinase 1 and 2 (ERK1/2) cascade in cardiomyocytes using the framework to find efficient adjustment screws for this cascade that is important for cardiomyocyte survival and maladaptive heart muscle growth. We modeled optimal pharmacological intervention points that are beneficial for the heart, but avoid the occurrence of a maladaptive ERK1/2 modification, the autophosphorylation of ERK at threonine 188 (ERK\(^{Thr188}\) phosphorylation), which causes cardiac hypertrophy. For this purpose, a network of a cardiomyocyte that was fitted to experimental data was equipped with external stimuli that model the pharmacological intervention points. Specifically, two situations were considered. In the first one, the cardiomyocyte was driven to a desired expression level with different treatment strategies. These strategies were quantified with respect to beneficial effects and maleficent side effects and then which one is the best treatment strategy was evaluated. In the second situation, it was shown how to model constitutively activated pathways and how to identify drug targets to obtain a desired activity level that is associated with a healthy state and in contrast to the maleficent expression pattern caused by the constitutively activated pathway. An implementation of the algorithms used for the calculations is also presented in this paper, which simplifies the application of the presented framework for drug targeting, optimal drug combinations and the systematic and automatic search for pharmacological intervention points. The codes were designed such that they can be combined with any mathematical model given by ordinary differential equations.},
  language  = {en}
}
@article{JaiteBuehrenDahmenetal.2019,
  author    = {Jaite, Charlotte and B{\"u}hren, Katharina and Dahmen, Brigitte and Dempfle, Astrid and Becker, Katja and Correll, Christoph U. and Egberts, Karin M. and Ehrlich, Stefan and Fleischhaker, Christian and von Gontard, Alexander and Hahn, Freia and Kolar, David and Kaess, Michael and Legenbauer, Tanja and Renner, Tobias J. and Schulze, Ulrike and Sinzig, Judith and Thomae, Ellen and Weber, Linda and Wessing, Ida and Antony, Gisela and Hebebrand, Johannes and F{\"o}cker, Manuel and Herpertz-Dahlmann, Beate},
  title     = {Clinical Characteristics of Inpatients with Childhood vs. Adolescent Anorexia Nervosa},
  series = {Nutrients},
  volume    = {11},
  journal   = {Nutrients},
  number    = {11},
  issn      = {2072-6643},
  doi       = {10.3390/nu11112593},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-193160},
  pages     = {2593},
  year      = {2019},
  abstract  = {We aimed to compare the clinical data at first presentation to inpatient treatment of children (<14 years) vs. adolescents (≥14 years) with anorexia nervosa (AN), focusing on duration of illness before hospital admission and body mass index (BMI) at admission and discharge, proven predictors of the outcomes of adolescent AN. Clinical data at first admission and at discharge in 289 inpatients with AN (children: n = 72; adolescents: n = 217) from a German multicenter, web-based registry for consecutively enrolled patients with childhood and adolescent AN were analyzed. Inclusion criteria were a maximum age of 18 years, first inpatient treatment due to AN, and a BMI <10th BMI percentile at admission. Compared to adolescents, children with AN had a shorter duration of illness before admission (median: 6.0 months vs. 8.0 months, p = 0.004) and higher BMI percentiles at admission (median: 0.7 vs. 0.2, p = 0.004) as well as at discharge (median: 19.3 vs. 15.1, p = 0.011). Thus, in our study, children with AN exhibited clinical characteristics that have been associated with better outcomes, including higher admission and discharge BMI percentile. Future studies should examine whether these factors are actually associated with positive long-term outcomes in children.},
  language  = {en}
}
@article{ThiessMellerupBraunschweig2019,
  author    = {Thiess, Torsten and Mellerup, Soren K. and Braunschweig, Holger},
  title     = {B-B Cleavage and Ring-Expansion of a 1,4,2,3-Diazadiborinine with N-Heterocyclic Carbenes},
  series = {Chemistry - A European Journal},
  volume    = {25},
  journal   = {Chemistry - A European Journal},
  number    = {59},
  doi       = {10.1002/chem.201903259},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-206173},
  pages     = {13572-13578},
  year      = {2019},
  abstract  = {A 1,4,2,3-diazadiborinine derivative was found to form Lewis adducts with strong two-electron donors such as N-heterocyclic and cyclic (alkyl)(amino)carbenes. Depending on the donor, some of these Lewis pairs are thermally unstable, converting to sole B,N-embedded products upon gentle heating. The products of these reactions, which have been fully characterized by NMR spectroscopy, elemental analysis, and single-crystal X-ray diffraction, were identified as B,N-heterocycles with fused 1,5,2,4-diazadiborepine and 1,4,2-diazaborinine rings. Computational modelling of the reaction mechanism provides insight into the formation of these unique structures, suggesting that a series of B-H, C-N, and B-B bond activation steps are responsible for these "intercalation" reactions between the 1,4,2,3-diazadiborinine and NHCs.},
  language  = {en}
}
@article{OPUS4-31955,
  title     = {Search for light resonances decaying to boosted quark pairs and produced in association with a photon or a jet in proton-proton collisions at root s=13 TeV with the ATLAS detector},
  series = {Physics Letters B},
  volume    = {788},
  journal   = {Physics Letters B},
  organization    = {The ATLAS Collaboration},
  doi       = {10.1016/j.physletb.2018.09.062},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-319552},
  pages     = {316-335},
  year      = {2019},
  abstract  = {This Letter presents a search for new light resonances decaying to pairs of quarks and produced in association with a high-p(T) photon or jet. The dataset consists of proton-proton collisions with an integrated luminosity of 36.1 fb(-1) at a centre-of-mass energy of root s = 13 TeV recorded by the ATLAS detector at the Large Hadron Collider. Resonance candidates are identified as massive large-radius jets with substructure consistent with a particle decaying into a quark pair. The mass spectrum of the candidates is examined for local excesses above background. No evidence of a new resonance is observed in the data, which are used to exclude the production of a lepto-phobic axial-vector Z' boson. (C) 2018 The Author(s). Published by Elsevier B.V.},
  language  = {en}
}
@article{LewitzkiKlementKosmalaetal.2019,
  author    = {Lewitzki, Victor and Klement, Rainer J. and Kosmala, Rebekka and Lisowski, Dominik and Flentje, Michael and Polat, B{\"u}lent},
  title     = {Accelerated hyperfractionated radiochemotherapy with temozolomide is equivalent to normofractionated radiochemotherapy in a retrospective analysis of patients with glioblastoma},
  series = {Radiation Oncology},
  volume    = {14},
  journal   = {Radiation Oncology},
  doi       = {10.1186/s13014-019-1427-5},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-202614},
  pages     = {227},
  year      = {2019},
  abstract  = {Background Current standard of treatment for newly diagnosed patients with glioblastoma (GBM) is surgical resection with adjuvant normofractionated radiotherapy (NFRT) combined with temozolomide (TMZ) chemotherapy. Hyperfractionated accelerated radiotherapy (HFRT) which was known as an option from randomized controlled trials before the temozolomide era has not been compared to the standard therapy in a randomized setting combined with TMZ. Methods Data of 152 patients with newly diagnosed GBM treated from 10/2004 until 7/2018 at a single tertiary care institution were extracted from a clinical database and retrospectively analyzed. Thirty-eight patients treated with NFRT of 60 Gy in 30 fractions (34 with simultaneous and 2 with sequential TMZ) were compared to 114 patients treated with HFRT of 54.0 Gy in 30 fraction of 1.8 Gy twice daily (109 with simultaneous and 3 with sequential TMZ). The association between treatment protocol and other variables with overall survival (OS) was assessed using univariable and multivariable Cox regression analysis; the latter was performed using variables selected by the LASSO method. Results Median overall survival (OS) was 20.3 month for the entire cohort. For patients treated with NFRT median OS was 24.4 months compared to 18.5 months in patients treated with HFRT (p = 0.131). In univariable regression analysis the use of dexamethasone during radiotherapy had a significant negative impact on OS in both patient groups, HR 2.21 (95\% CI 1.47-3.31, p = 0.0001). In multivariable analysis adjusted for O6-methylguanine-DNA methyl-transferase (MGMT) promotor methylation status, salvage treatment and secondary GBM, the use of dexamethasone was still a negative prognostic factor, HR 1.95 (95\% CI 1.21-3.13, p = 0.006). Positive MGMT-methylation status and salvage treatment were highly significant positive prognostic factors. There was no strong association between treatment protocol and OS (p = 0.504). Conclusions Our retrospective analysis supports the hypothesis of equivalence between HFRT and the standard protocol of treatment for GBM. For those patients who are willing to obtain the benefit of shortening the course of radiochemotherapy, HFRT may be an alternative with comparable efficacy although it was not yet tested in a large prospective randomized study against the current standard. The positive influence of salvage therapy and negative impact of concomitant use of corticosteroids should be addressed in future prospective trials. To confirm our results, we plan to perform a pooled analysis with other tertiary clinics in order to achieve better statistical reliability.},
  language  = {en}
}
@article{SeidlmayerMagesBerbneretal.2019,
  author    = {Seidlmayer, Lea K. and Mages, Christine and Berbner, Annette and Eder-Negrin, Petra and Arias-Loza, Paula Anahi and Kaspar, Mathias and Song, Moshi and Dorn, Gerald W. and Kohlhaas, Michael and Frantz, Stefan and Maack, Christoph and Gerull, Brenda and Dedkova, Elena N.},
  title     = {Mitofusin 2 is essential for IP3-mediated SR/Mitochondria metabolic feedback in ventricular myocytes},
  series = {Frontiers in Physiology},
  volume    = {10},
  journal   = {Frontiers in Physiology},
  number    = {733},
  issn      = {1664-042X},
  doi       = {10.3389/fphys.2019.00733},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-199141},
  year      = {2019},
  abstract  = {Aim: Endothelin-1 (ET-1) and angiotensin II (Ang II) are multifunctional peptide hormones that regulate the function of the cardiovascular and renal systems. Both hormones increase the intracellular production of inositol-1,4,5-trisphosphate (IP\(_3\)) by activating their membrane-bound receptors. We have previously demonstrated that IP\(_3\)-mediated sarcoplasmic reticulum (SR) Ca\(^{2+}\) release results in mitochondrial Ca\(^{2+}\) uptake and activation of ATP production. In this study, we tested the hypothesis that intact SR/mitochondria microdomains are required for metabolic IP\(_3\)-mediated SR/mitochondrial feedback in ventricular myocytes. Methods: As a model for disrupted mitochondrial/SR microdomains, cardio-specific tamoxifen-inducible mitofusin 2 (Mfn2) knock out (KO) mice were used. Mitochondrial Ca\(^{2+}\) uptake, membrane potential, redox state, and ATP generation were monitored in freshly isolated ventricular myocytes from Mfn2 KO mice and their control wild-type (WT) littermates. Results: Stimulation of ET-1 receptors in healthy control myocytes increases mitochondrial Ca\(^{2+}\) uptake, maintains mitochondrial membrane potential and redox balance leading to the enhanced ATP generation. Mitochondrial Ca\(^{2+}\) uptake upon ET-1 stimulation was significantly higher in interfibrillar (IFM) and perinuclear (PNM) mitochondria compared to subsarcolemmal mitochondria (SSM) in WT myocytes. Mfn2 KO completely abolished mitochondrial Ca\(^{2+}\) uptake in IFM and PNM mitochondria but not in SSM. However, mitochondrial Ca2+ uptake induced by beta-adrenergic receptors activation with isoproterenol (ISO) was highest in SSM, intermediate in IFM, and smallest in PNM regions. Furthermore, Mfn2 KO did not affect ISO-induced mitochondrial Ca\(^{2+}\) uptake in SSM and IFM mitochondria; however, enhanced mitochondrial Ca\(^{2+}\) uptake in PNM. In contrast to ET-1, ISO induced a decrease in ATP levels in WT myocytes. Mfn2 KO abolished ATP generation upon ET-1 stimulation but increased ATP levels upon ISO application with highest levels observed in PNM regions. Conclusion: When the physical link between SR and mitochondria by Mfn2 was disrupted, the SR/mitochondrial metabolic feedback mechanism was impaired resulting in the inability of the IP\(_3\)-mediated SR Ca\(^{2+}\) release to induce ATP production in ventricular myocytes from Mfn2 KO mice. Furthermore, we revealed the difference in Mfn2-mediated SR-mitochondrial communication depending on mitochondrial location and type of communication (IP\(_3\)R-mRyR1 vs. ryanodine receptor type 2-mitochondrial calcium uniporter).},
  language  = {en}
}
@article{LandmanLauth2019,
  author    = {Landman, Todd and Lauth, Hans-Joachim},
  title     = {Political Trade-Offs: Democracy and Governance in a Changing World},
  series = {Politics and Governance},
  volume    = {7},
  journal   = {Politics and Governance},
  number    = {4},
  issn      = {2183-2463},
  doi       = {10.17645/pag.v7i4.2642},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-144308},
  pages     = {237-242},
  year      = {2019},
  abstract  = {The investigation of trade-offs in political science receives only limited attention, although many scholars acknowledge the importance of trade-offs across a variety of different areas. A systematic and comprehensive examination of the topic is missing. This thematic issue of Politics and Governance sheds light on this research deficit by providing a holistic but also an integrative view on trade-offs in the political realm for the first time. Researchers of trade-offs from different political areas present and discuss their findings, and promote a fruitful exchange, which overcomes the current isolation of the approaches. They consider the theoretical and methodological questions as well as the identification of empirical tradeoffs. Furthermore, they provide insights into the possibility to balance trade-offs and strategies, which could help actors to find such compromises.},
  language  = {en}
}
@article{SchuhmannStollBohretal.2019,
  author    = {Schuhmann, Michael K. and Stoll, Guido and Bohr, Arne and Volkmann, Jens and Fluri, Felix},
  title     = {Electrical stimulation of the mesencephalic locomotor region attenuates neuronal loss and cytokine expression in the perifocal region of photothrombotic stroke in rats},
  series = {International Journal of Molecular Science},
  volume    = {20},
  journal   = {International Journal of Molecular Science},
  number    = {9},
  issn      = {1422-0067},
  doi       = {10.3390/ijms20092341},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-201355},
  year      = {2019},
  abstract  = {Deep brain stimulation of the mesencephalic locomotor region (MLR) improves the motor symptoms in Parkinson's disease and experimental stroke by intervening in the motor cerebral network. Whether high-frequency stimulation (HFS) of the MLR is involved in non-motor processes, such as neuroprotection and inflammation in the area surrounding the photothrombotic lesion, has not been elucidated. This study evaluates whether MLR-HFS exerts an anti-apoptotic and anti-inflammatory effect on the border zone of cerebral photothrombotic stroke. Rats underwent photothrombotic stroke of the right sensorimotor cortex and the implantation of a microelectrode into the ipsilesional MLR. After intervention, either HFS or sham stimulation of the MLR was applied for 24 h. The infarct volumes were calculated from consecutive brain sections. Neuronal apoptosis was analyzed by TUNEL staining. Flow cytometry and immunohistochemistry determined the perilesional inflammatory response. Neuronal apoptosis was significantly reduced in the ischemic penumbra after MLR-HFS, whereas the infarct volumes did not differ between the groups. MLR-HFS significantly reduced the release of cytokines and chemokines within the ischemic penumbra. MLR-HFS is neuroprotective and it reduces pro-inflammatory mediators in the area that surrounds the photothrombotic stroke without changing the number of immune cells, which indicates that MLR-HFS enables the function of inflammatory cells to be altered on a molecular level.},
  language  = {en}
}
@article{RadchukRajivPotokinaetal.2019,
  author    = {Radchuk, Volodymyr and Rajiv, Sharma and Potokina, Elena and Radchuk, Ruslana and Weier, Diana and Munz, Eberhard and Schreiber, Miriam and Mascher, Martin and Stein, Nils and Wicker, Thomas and Kilian, Benjamin and Borisjuk, Ljudmilla},
  title     = {The highly divergent \(Jekyll\) genes, required for sexual reproduction, are lineage specific for the related grass tribes Triticeae and Bromeae},
  series = {Plant Journal},
  volume    = {98},
  journal   = {Plant Journal},
  number    = {6},
  doi       = {10.1111/tpj.14363},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-224769},
  pages     = {961-974},
  year      = {2019},
  abstract  = {Phylogenetically related groups of species contain lineage-specific genes that exhibit no sequence similarity to any genes outside the lineage. We describe here that the Jekyll gene, required for sexual reproduction, exists in two much diverged allelic variants, Jek1 and Jek3. Despite low similarity, the Jek1 and Jek3 proteins share identical signal peptides, conserved cysteine positions and direct repeats. The Jek1/Jek3 sequences are located at the same chromosomal locus and inherited in a monogenic Mendelian fashion. Jek3 has a similar expression as Jek1 and complements the Jek1 function in Jek1-deficient plants. Jek1 and Jek3 allelic variants were almost equally distributed in a collection of 485 wild and domesticated barley accessions. All domesticated barleys harboring the Jek1 allele belong to single haplotype J1-H1 indicating a genetic bottleneck during domestication. Domesticated barleys harboring the Jek3 allele consisted of three haplotypes. Jekyll-like sequences were found only in species of the closely related tribes Bromeae and Triticeae but not in other Poaceae. Non-invasive magnetic resonance imaging revealed intrinsic grain structure in Triticeae and Bromeae, associated with the Jekyll function. The emergence of Jekyll suggests its role in the separation of the Bromeae and Triticeae lineages within the Poaceae and identifies the Jekyll genes as lineage-specific.},
  language  = {en}
}
@article{RaynerColemanPurvesetal.2019,
  author    = {Rayner, Christopher and Coleman, Jonathan R. I. and Purves, Kirstin L. and Hodsoll, John and Goldsmith, Kimberley and Alpers, Georg W. and Andersson, Evelyn and Arolt, Volker and Boberg, Julia and B{\"o}gels, Susan and Creswell, Cathy and Cooper, Peter and Curtis, Charles and Deckert, J{\"u}rgen and Domschke, Katharina and El Alaoui, Samir and Fehm, Lydia and Fydrich, Thomas and Gerlach, Alexander L. and Grocholewski, Anja and Hahlweg, Kurt and Hamm, Alfons and Hedman, Erik and Heiervang, Einar R. and Hudson, Jennifer L. and J{\"o}hren, Peter and Keers, Robert and Kircher, Tilo and Lang, Thomas and Lavebratt, Catharina and Lee, Sang-hyuck and Lester, Kathryn J. and Lindefors, Nils and Margraf, J{\"u}rgen and Nauta, Maaike and Pan{\´e}-Farr{\´e}, Christiane A. and Pauli, Paul and Rapee, Ronald M. and Reif, Andreas and Rief, Winfried and Roberts, Susanna and Schalling, Martin and Schneider, Silvia and Silverman, Wendy K. and Str{\"o}hle, Andreas and Teismann, Tobias and Thastum, Mikael and Wannem{\"u}ller, Andre and Weber, Heike and Wittchen, Hans-Ulrich and Wolf, Christiane and R{\"u}ck, Christian and Breen, Gerome and Eley, Thalia C.},
  title     = {A genome-wide association meta-analysis of prognostic outcomes following cognitive behavioural therapy in individuals with anxiety and depressive disorders},
  series = {Translational Psychiatry},
  volume    = {9},
  journal   = {Translational Psychiatry},
  number    = {150},
  doi       = {10.1038/s41398-019-0481-y},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-225048},
  pages     = {1-13},
  year      = {2019},
  abstract  = {Major depressive disorder and the anxiety disorders are highly prevalent, disabling and moderately heritable. Depression and anxiety are also highly comorbid and have a strong genetic correlation (r(g) approximate to 1). Cognitive behavioural therapy is a leading evidence-based treatment but has variable outcomes. Currently, there are no strong predictors of outcome. Therapygenetics research aims to identify genetic predictors of prognosis following therapy. We performed genome-wide association meta-analyses of symptoms following cognitive behavioural therapy in adults with anxiety disorders (n = 972), adults with major depressive disorder (n = 832) and children with anxiety disorders (n = 920; meta-analysis n = 2724). We (h(SNP)(2)) and polygenic scoring was used to examine genetic associations between therapy outcomes and psychopathology, personality and estimated the variance in therapy outcomes that could be explained by common genetic variants learning. No single nucleotide polymorphisms were strongly associated with treatment outcomes. No significant estimate of h(SNP)(2) could be obtained, suggesting the heritability of therapy outcome is smaller than our analysis was powered to detect. Polygenic scoring failed to detect genetic overlap between therapy outcome and psychopathology, personality or learning. This study is the largest therapygenetics study to date. Results are consistent with previous, similarly powered genome-wide association studies of complex traits.},
  language  = {en}
}
@article{SchlegelPetersDooseetal.2019,
  author    = {Schlegel, Jan and Peters, Simon and Doose, S{\"o}ren and Schubert-Unkmeir, Alexandra and Sauer, Markus},
  title     = {Super-resolution microscopy reveals local accumulation of plasma membrane gangliosides at Neisseria meningitidis Invasion Sites},
  series = {Frontiers in Cell and Developmental Biology},
  volume    = {7},
  journal   = {Frontiers in Cell and Developmental Biology},
  number    = {194},
  doi       = {10.3389/fcell.2019.00194},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-201639},
  year      = {2019},
  abstract  = {Neisseria meningitidis (meningococcus) is a Gram-negative bacterium responsible for epidemic meningitis and sepsis worldwide. A critical step in the development of meningitis is the interaction of bacteria with cells forming the blood-cerebrospinal fluid barrier, which requires tight adhesion of the pathogen to highly specialized brain endothelial cells. Two endothelial receptors, CD147 and the β2-adrenergic receptor, have been found to be sequentially recruited by meningococci involving the interaction with type IV pilus. Despite the identification of cellular key players in bacterial adhesion the detailed mechanism of invasion is still poorly understood. Here, we investigated cellular dynamics and mobility of the type IV pilus receptor CD147 upon treatment with pili enriched fractions and specific antibodies directed against two extracellular Ig-like domains in living human brain microvascular endothelial cells. Modulation of CD147 mobility after ligand binding revealed by single-molecule tracking experiments demonstrates receptor activation and indicates plasma membrane rearrangements. Exploiting the binding of Shiga (STxB) and Cholera toxin B (CTxB) subunits to the two native plasma membrane sphingolipids globotriaosylceramide (Gb3) and raft-associated monosialotetrahexosylganglioside GM1, respectively, we investigated their involvement in bacterial invasion by super-resolution microscopy. Structured illumination microscopy (SIM) and direct stochastic optical reconstruction microscopy (dSTORM) unraveled accumulation and coating of meningococci with GM1 upon cellular uptake. Blocking of CTxB binding sites did not impair bacterial adhesion but dramatically reduced bacterial invasion efficiency. In addition, cell cycle arrest in G1 phase induced by serum starvation led to an overall increase of GM1 molecules in the plasma membrane and consequently also in bacterial invasion efficiency. Our results will help to understand downstream signaling events after initial type IV pilus-host cell interactions and thus have general impact on the development of new therapeutics targeting key molecules involved in infection.},
  language  = {en}
}
@article{KleefeldtBoemmelBroedeetal.2019,
  author    = {Kleefeldt, Florian and B{\"o}mmel, Heike and Broede, Britta and Thomsen, Michael and Pfeiffer, Verena and W{\"o}rsd{\"o}rfer, Philipp and Karnati, Srikanth and Wagner, Nicole and Rueckschloss, Uwe and Erg{\"u}n, S{\"u}leyman},
  title     = {Aging-related carcinoembryonic antigen-related cell adhesion molecule 1 signaling promotes vascular dysfunction},
  series = {Aging Cell},
  volume    = {2019},
  journal   = {Aging Cell},
  number    = {18},
  doi       = {10.1111/acel.13025},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-201231},
  pages     = {e13025},
  year      = {2019},
  abstract  = {Aging is an independent risk factor for cardiovascular diseases and therefore of particular interest for the prevention of cardiovascular events. However, the mechanisms underlying vascular aging are not well understood. Since carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is crucially involved in vascular homeostasis, we sought to identify the role of CEACAM1 in vascular aging. Using human internal thoracic artery and murine aorta, we show that CEACAM1 is upregulated in the course of vascular aging. Further analyses demonstrated that TNF-α is CEACAM1-dependently upregulated in the aging vasculature. Vice versa, TNF-α induces CEACAM1 expression. This results in a feed-forward loop in the aging vasculature that maintains a chronic pro-inflammatory milieu. Furthermore, we demonstrate that age-associated vascular alterations, that is, increased oxidative stress and vascular fibrosis, due to increased medial collagen deposition crucially depend on the presence of CEACAM1. Additionally, age-dependent upregulation of vascular CEACAM1 expression contributes to endothelial barrier impairment, putatively via increased VEGF/VEGFR-2 signaling. Consequently, aging-related upregulation of vascular CEACAM1 expression results in endothelial dysfunction that may promote atherosclerotic plaque formation in the presence of additional risk factors. Our data suggest that CEACAM1 might represent an attractive target in order to delay physiological aging and therefore the transition to vascular disorders such as atherosclerosis.},
  language  = {en}
}
@article{RuboGamer2019,
  author    = {Rubo, Marius and Gamer, Matthias},
  title     = {Visuo-tactile congruency influences the body schema during full body ownership illusion},
  series = {Consciousness and Cognition},
  volume    = {73},
  journal   = {Consciousness and Cognition},
  doi       = {10.1016/j.concog.2019.05.006},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-227095},
  pages     = {UNSP 102758, 1-14},
  year      = {2019},
  abstract  = {Previous research showed that full body ownership illusions in virtual reality (VR) can be robustly induced by providing congruent visual stimulation, and that congruent tactile experiences provide a dispensable extension to an already established phenomenon. Here we show that visuo-tactile congruency indeed does not add to already high measures for body ownership on explicit measures, but does modulate movement behavior when walking in the laboratory. Specifically, participants who took ownership over a more corpulent virtual body with intact visuo-tactile congruency increased safety distances towards the laboratory's walls compared to participants who experienced the same illusion with deteriorated visuo-tactile congruency. This effect is in line with the body schema more readily adapting to a more corpulent body after receiving congruent tactile information. We conclude that the action-oriented, unconscious body schema relies more heavily on tactile information compared to more explicit aspects of body ownership.},
  language  = {en}
}
@article{NeugebauerSchneiderKollmar2019,
  author    = {Neugebauer, Hermann and Schneider, Hauke and Kollmar, Rainer},
  title     = {Letter by Neugebauer et al. regarding article "Hypothermia after decompressive hemicraniectomy in treatment of malignant middle cerebral artery stroke: comment on the randomized clinical trial"},
  series = {Critical Care},
  volume    = {23},
  journal   = {Critical Care},
  doi       = {10.1186/s13054-019-2600-9},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-232268},
  year      = {2019},
  abstract  = {No abstract available.},
  language  = {en}
}
@article{KoenigPechmannThieleetal.2019,
  author    = {K{\"o}nig, Kirsten and Pechmann, Astrid and Thiele, Simone and Walter, Maggie C. and Schorling, David and Tassoni, Adrian and Lochm{\"u}ller, Hanns and M{\"u}ller-Reible, Clemens and Kirschner, Janbernd},
  title     = {De-duplicating patient records from three independent data sources reveals the incidence of rare neuromuscular disorders in Germany},
  series = {Orphanet Journal of Rare Diseases},
  volume    = {14},
  journal   = {Orphanet Journal of Rare Diseases},
  doi       = {10.1186/s13023-019-1125-2},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-222807},
  year      = {2019},
  abstract  = {Background Estimation of incidence in rare diseases is often challenging due to unspecific and incomplete coding and recording systems. Patient- and health care provider-driven data collections are held with different organizations behind firewalls to protect the privacy of patients. They tend to be fragmented, incomplete and their aggregation leads to further inaccuracies, as the duplicated records cannot easily be identified. We here report about a novel approach to evaluate the incidences of Duchenne muscular dystrophy (DMD) and spinal muscular atrophy (SMA) in Germany. Methods We performed a retrospective epidemiological study collecting data from patients with dystrophinopathies (DMD and Becker muscular dystrophy) and SMA born between 1995 and 2018. We invited all neuromuscular centers, genetic institutes and the patient registries for DMD and SMA in Germany to participate in the data collection. A novel web-based application for data entry was developed converting patient identifying information into a hash code. Duplicate entries were reliably allocated to the distinct patient. Results We collected 5409 data entries in our web-based database representing 1955 distinct patients with dystrophinopathies and 1287 patients with SMA. 55.0\% of distinct patients were found in one of the 3 data sources only, while 32.0\% were found in 2, and 13.0\% in all 3 data sources. The highest number of SMA patients was reported by genetic testing laboratories, while for DMD the highest number was reported by the clinical specialist centers. After the removal of duplicate records, the highest yearly incidence for DMD was calculated as 2.57:10,000 in 2001 and the highest incidence for SMA as 1.36:10,000 in 2014. Conclusion With our novel approach (compliant with data protection regulations), we were able to identify unique patient records and estimate the incidence of DMD and SMA in Germany combining and de-duplicating data from patient registries, genetic institutes, and clinical care centers. Although we combined three different data sources, an unknown number of patients might not have been reported by any of these sources. Therefore, our results reflect the minimal incidence of these diseases.},
  language  = {en}
}
@article{SepahiFaustSturmetal.2019,
  author    = {Sepahi, Ilnaz and Faust, Ulrike and Sturm, Marc and Bosse, Kristin and Kehrer, Martin and Heinrich, Tilman and Grundman-Hauser, Kathrin and Bauer, Peter and Ossowski, Stephan and Susak, Hana and Varon, Raymonda and Schr{\"o}ck, Evelin and Niederacher, Dieter and Auber, Bernd and Sutter, Christian and Arnold, Norbert and Hahnen, Eric and Dworniczak, Bernd and Wang-Gorke, Shan and Gehrig, Andrea and Weber, Bernhard H. F. and Engel, Christoph and Lemke, Johannes R. and Hartkopf, Andreas and Huu Phuc, Nguyen and Riess, Olaf and Schroeder, Christopher},
  title     = {Investigating the effects of additional truncating variants in DNA-repair genes on breast cancer risk in BRCA1-positive women},
  series = {BMC Cancer},
  volume    = {19},
  journal   = {BMC Cancer},
  doi       = {10.1186/s12885-019-5946-0},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-237676},
  year      = {2019},
  abstract  = {Background Inherited pathogenic variants in BRCA1 and BRCA2 are the most common causes of hereditary breast and ovarian cancer (HBOC). The risk of developing breast cancer by age 80 in women carrying a BRCA1 pathogenic variant is 72\%. The lifetime risk varies between families and even within affected individuals of the same family. The cause of this variability is largely unknown, but it is hypothesized that additional genetic factors contribute to differences in age at onset (AAO). Here we investigated whether truncating and rare missense variants in genes of different DNA-repair pathways contribute to this phenomenon. Methods We used extreme phenotype sampling to recruit 133 BRCA1-positive patients with either early breast cancer onset, below 35 (early AAO cohort) or cancer-free by age 60 (controls). Next Generation Sequencing (NGS) was used to screen for variants in 311 genes involved in different DNA-repair pathways. Results Patients with an early AAO (73 women) had developed breast cancer at a median age of 27 years (interquartile range (IQR); 25.00-27.00 years). A total of 3703 variants were detected in all patients and 43 of those (1.2\%) were truncating variants. The truncating variants were found in 26 women of the early AAO group (35.6\%; 95\%-CI 24.7 - 47.7\%) compared to 16 women of controls (26.7\%; 95\%-CI 16.1 to 39.7\%). When adjusted for environmental factors and family history, the odds ratio indicated an increased breast cancer risk for those carrying an additional truncating DNA-repair variant to BRCA1 mutation (OR: 3.1; 95\%-CI 0.92 to 11.5; p-value = 0.07), although it did not reach the conventionally acceptable significance level of 0.05. Conclusions To our knowledge this is the first time that the combined effect of truncating variants in DNA-repair genes on AAO in patients with hereditary breast cancer is investigated. Our results indicate that co-occurring truncating variants might be associated with an earlier onset of breast cancer in BRCA1-positive patients. Larger cohorts are needed to confirm these results.},
  language  = {en}
}
@article{WiechmannRoehSaueretal.2019,
  author    = {Wiechmann, Tobias and R{\"o}h, Simone and Sauer, Susann and Czamara, Darina and Arloth, Janine and K{\"o}del, Maik and Beintner, Madita and Knop, Lisanne and Menke, Andreas and Binder, Elisabeth B. and Proven{\c{c}}al, Nadine},
  title     = {Identification of dynamic glucocorticoid-induced methylation changes at the FKBP5 locus},
  series = {Clinical Epigenetics},
  volume    = {11},
  journal   = {Clinical Epigenetics},
  doi       = {10.1186/s13148-019-0682-5},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-233673},
  year      = {2019},
  abstract  = {Background Epigenetic mechanisms may play a major role in the biological embedding of early-life stress (ELS). One proposed mechanism is that glucocorticoid (GC) release following ELS exposure induces long-lasting alterations in DNA methylation (DNAm) of important regulatory genes of the stress response. Here, we investigate the dynamics of GC-dependent methylation changes in key regulatory regions of the FKBP5 locus in which ELS-associated DNAm changes have been reported. Results We repeatedly measured DNAm in human peripheral blood samples from 2 independent cohorts exposed to the GC agonist dexamethasone (DEX) using a targeted bisulfite sequencing approach, complemented by data from Illumina 450K arrays. We detected differentially methylated CpGs in enhancers co-localizing with GC receptor binding sites after acute DEX treatment (1 h, 3 h, 6 h), which returned to baseline levels within 23 h. These changes withstood correction for immune cell count differences. While we observed main effects of sex, age, body mass index, smoking, and depression symptoms on FKBP5 methylation levels, only the functional FKBP5 SNP (rs1360780) moderated the dynamic changes following DEX. This genotype effect was observed in both cohorts and included sites previously shown to be associated with ELS. Conclusion Our study highlights that DNAm levels within regulatory regions of the FKBP5 locus show dynamic changes following a GC challenge and suggest that factors influencing the dynamics of this regulation may contribute to the previously reported alterations in DNAm associated with current and past ELS exposure.},
  language  = {en}
}