TY - JOUR A1 - Kleih-Dahms, Sonja Christina A1 - Botrel, Loic A1 - Kübler, Andrea T1 - The influence of motivation and emotion on sensorimotor rhythm-based brain-computer interface performance JF - Psychophysiology N2 - While decades of research have investigated and technically improved brain–computer interface (BCI)-controlled applications, relatively little is known about the psychological aspects of brain–computer interfacing. In 35 healthy students, we investigated whether extrinsic motivation manipulated via monetary reward and emotional state manipulated via video and music would influence behavioral and psychophysiological measures of performance with a sensorimotor rhythm (SMR)-based BCI. We found increased task-related brain activity in extrinsically motivated (rewarded) as compared with nonmotivated participants but no clear effect of emotional state manipulation. Our experiment investigated the short-term effect of motivation and emotion manipulation in a group of young healthy subjects, and thus, the significance for patients in the locked-in state, who may be in need of a BCI, remains to be investigated. KW - brain-computer interface KW - sensorimotor rhythm KW - psychological variables KW - motivation KW - emotional state KW - electroencephalogram Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-259664 VL - 58 IS - 8 ER - TY - THES A1 - Mokay-Rinke, Shiloe Marie T1 - The Integration of Female Refugees in Germany: Perspectives of Women and an Analysis of Federal and Selected State and City Integration Policies from 1998 to 2019 T1 - Die Integration geflüchteter Frauen in Deutschland: Sichtweisen der Betroffenen und eine Analyse der Integrationspolitik des Bundes und ausgewählter Bundesländer und Städte zwischen 1998 und 2019 N2 - The following study, The Integration of Female Refugees in Germany: Perspectives of Women and an Analysis of Federal and Selected State and City Integration Policies from 1998-2019, is focused on the qualitative analysis of integration policy in Germany regarding female refugees. The states of North Rhine-Westphalia, Bavaria, and Saxony-Anhalt have been selected for this dissertation as well as the cities of Cologne, Wuerzburg, and Magdeburg. Through an analysis and comparison of integration policies and programs on the federal and selected state and city levels the question will be answered how recognized female refugees are taken into account with the development and formulation of integration policy in Germany. The analysis is then complemented through interviews with recognized female refugees in each of the states and cities. Through analyzing the results of the interviews the question will be answered how the women view their situation and integration. Through a comparison of the findings from the policy analysis and the interviews it will then be able to decipher if integration policies and programs are truly reaching their target group, if they are effective, or what hurdles they may be producing. The goal of the study is to provide initial findings on the overall integration of recognized female refugees in Germany in connection to integration policies in order to discover potential deficits or ineffective programs and policies which can then be further researched in order to produce concrete policy suggestions. N2 - Die vorliegende Arbeit – Die Integration geflüchteter Frauen in Deutschland: Sichtweisen der Betroffenen und eine Analyse der Integrationspolitik des Bundes und ausgewählter Bundesländer und Städte zwischen 1998 und 2019 – analysiert qualitativ die Integrationspolitik Deutschlands bezüglich geflüchteter Frauen. Neben der Bundesebene wurden für eine Analyse auf Landesebene Nordrhein-Westfalen, Bayern und Sachsen-Anhalt sowie auf kommunaler Ebene Köln, Würzburg und Magdeburg beispielhaft untersucht. Durch diesen Vergleich von Gesetzen, Richtlinien und Programmen wird die Frage beantwortet, wie anerkannte geflüchtete Frauen und deren Perspektive bei der Ausgestaltung von Integrationsstrategien berücksichtigt werden. Die Analyse wird vervollständigt durch die Ergebnisse von Interviews mit anerkannten geflüchteten Frauen in den untersuchten Städten und Bundesländern. Dadurch wird die Frage beantwortet, wie die Betroffenen selbst ihren Integrationserfolg und ihre derzeitige Situation einschätzen. Durch einen Vergleich der Ergebnisse der Analyse der Integrationspolitik und der Ergebnisse der Interviews wird dann eine Einschätzung ermöglicht, inwiefern die Ansätze der Integrationspolitik tatsächlich den Bedürfnissen der Zielgruppe entsprechen, ob sie effektiv sind oder welche Schwierigkeiten sie den Betroffenen bereiten können. Das Ziel der vorliegenden Arbeit ist es, erste Einblicke zu gewinnen darüber, wie ziel- oder irreführend die bisherigen Ansätze und Richtlinien für die Integration anerkannter geflüchteter Frauen sind. Darauf aufbauend könnten folgende Studien sich verstärkt mit dem Thema beschäftigen, um letztendlich konkrete Vorschläge für eine effektivere Integrationspolitik hervorbringen zu können. KW - Organisation KW - Integration KW - Refugees KW - Female Refugees KW - Integration Policy Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-243047 ER - TY - JOUR A1 - Petruseva, Irina A1 - Naumenko, Natalia A1 - Kuper, Jochen A1 - Anarbaev, Rashid A1 - Kappenberger, Jeannette A1 - Kisker, Caroline A1 - Lavrik, Olga T1 - The Interaction Efficiency of XPD-p44 With Bulky DNA Damages Depends on the Structure of the Damage JF - Frontiers in Cell and Developmental Biology N2 - The successful elimination of bulky DNA damages via the nucleotide excision repair (NER) system is largely determined by the damage recognition step. This step consists of primary recognition and verification of the damage. The TFIIH helicase XPD plays a key role in the verification step during NER. To date, the mechanism of damage verification is not sufficiently understood and requires further detailed research. This study is a systematic investigation of the interaction of ctXPD (Chaetomium thermophilum) as well as ctXPD-ctp44 with model DNAs, which contain structurally different bulky lesions with previously estimated NER repair efficiencies. We have used ATPase and DNA binding studies to assess the interaction of ctXPD with damaged DNA. The result of the analysis of ctXPD-ctp44 binding to DNA containing fluorescent and photoactivatable lesions demonstrates the relationship between the affinity of XPD for DNAs containing bulky damages and the ability of the NER system to eliminate the damage. Photo-cross-linking of ctXPD with DNA probes containing repairable and unrepairable photoactivatable damages reveals differences in the DNA interaction efficiency in the presence and absence of ctp44. In general, the results obtained indicate the ability of ctXPD-ctp44 to interact with a damage and suggest a significant role for ctp44 subunit in the verification process. KW - nucleotide excision repair KW - XPD helicase KW - DNA damage KW - protein-DNA interaction KW - bulky damages recognition KW - photo-cross-linking Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-231806 SN - 2296-634X VL - 9 ER - TY - JOUR A1 - Budde, Heidi A1 - Hassoun, Roua A1 - Tangos, Melina A1 - Zhazykbayeva, Saltanat A1 - Herwig, Melissa A1 - Varatnitskaya, Marharyta A1 - Sieme, Marcel A1 - Delalat, Simin A1 - Sultana, Innas A1 - Kolijn, Detmar A1 - Gömöri, Kamilla A1 - Jarkas, Muhammad A1 - Lódi, Mária A1 - Jaquet, Kornelia A1 - Kovács, Árpád A1 - Mannherz, Hans Georg A1 - Sequeira, Vasco A1 - Mügge, Andreas A1 - Leichert, Lars I. A1 - Sossalla, Samuel A1 - Hamdani, Nazha T1 - The interplay between S-glutathionylation and phosphorylation of cardiac troponin I and myosin binding protein C in end-stage human failing hearts JF - Antioxidants N2 - Oxidative stress is defined as an imbalance between the antioxidant defense system and the production of reactive oxygen species (ROS). At low levels, ROS are involved in the regulation of redox signaling for cell protection. However, upon chronical increase in oxidative stress, cell damage occurs, due to protein, DNA and lipid oxidation. Here, we investigated the oxidative modifications of myofilament proteins, and their role in modulating cardiomyocyte function in end-stage human failing hearts. We found altered maximum Ca\(^{2+}\)-activated tension and Ca\(^{2+}\) sensitivity of force production of skinned single cardiomyocytes in end-stage human failing hearts compared to non-failing hearts, which was corrected upon treatment with reduced glutathione enzyme. This was accompanied by the increased oxidation of troponin I and myosin binding protein C, and decreased levels of protein kinases A (PKA)- and C (PKC)-mediated phosphorylation of both proteins. The Ca\(^{2+}\) sensitivity and maximal tension correlated strongly with the myofilament oxidation levels, hypo-phosphorylation, and oxidative stress parameters that were measured in all the samples. Furthermore, we detected elevated titin-based myocardial stiffness in HF myocytes, which was reversed by PKA and reduced glutathione enzyme treatment. Finally, many oxidative stress and inflammation parameters were significantly elevated in failing hearts compared to non-failing hearts, and corrected upon treatment with the anti-oxidant GSH enzyme. Here, we provide evidence that the altered mechanical properties of failing human cardiomyocytes are partially due to phosphorylation, S-glutathionylation, and the interplay between the two post-translational modifications, which contribute to the development of heart failure. KW - myofilament proteins KW - oxidative stress KW - inflammation KW - phosphorylation KW - S-glutathionylation Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-242701 SN - 2076-3921 VL - 10 IS - 7 ER - TY - JOUR A1 - Avota, Elita A1 - Bodem, Jochen A1 - Chithelen, Janice A1 - Mandasari, Putri A1 - Beyersdorf, Niklas A1 - Schneider-Schaulies, Jürgen T1 - The Manifold Roles of Sphingolipids in Viral Infections JF - Frontiers in Physiology N2 - Sphingolipids are essential components of eukaryotic cells. In this review, we want to exemplarily illustrate what is known about the interactions of sphingolipids with various viruses at different steps of their replication cycles. This includes structural interactions during entry at the plasma membrane or endosomal membranes, early interactions leading to sphingolipid-mediated signal transduction, interactions with internal membranes and lipids during replication, and interactions during virus assembly and budding. Targeted interventions in sphingolipid metabolism – as far as they can be tolerated by cells and organisms – may open novel possibilities to support antiviral therapies. Human immunodeficiency virus type 1 (HIV-1) infections have intensively been studied, but for other viral infections, such as influenza A virus (IAV), measles virus (MV), hepatitis C virus (HCV), dengue virus, Ebola virus, and severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), investigations are still in their beginnings. As many inhibitors of sphingolipid metabolism are already in clinical use against other diseases, repurposing studies for applications in some viral infections appear to be a promising approach. KW - sphingolipid KW - ceramide KW - sphingosine-1-phosphate KW - plasma membrane KW - virus entry KW - virus replication KW - virus budding Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-246975 SN - 1664-042X VL - 12 ER - TY - JOUR A1 - Paudel, Rupesh A1 - Fusi, Lorenza A1 - Schmidt, Marc T1 - The MEK5/ERK5 pathway in health and disease JF - International Journal of Molecular Sciences N2 - The MEK5/ERK5 mitogen-activated protein kinases (MAPK) cascade is a unique signaling module activated by both mitogens and stress stimuli, including cytokines, fluid shear stress, high osmolarity, and oxidative stress. Physiologically, it is mainly known as a mechanoreceptive pathway in the endothelium, where it transduces the various vasoprotective effects of laminar blood flow. However, it also maintains integrity in other tissues exposed to mechanical stress, including bone, cartilage, and muscle, where it exerts a key function as a survival and differentiation pathway. Beyond its diverse physiological roles, the MEK5/ERK5 pathway has also been implicated in various diseases, including cancer, where it has recently emerged as a major escape route, sustaining tumor cell survival and proliferation under drug stress. In addition, MEK5/ERK5 dysfunction may foster cardiovascular diseases such as atherosclerosis. Here, we highlight the importance of the MEK5/ERK5 pathway in health and disease, focusing on its role as a protective cascade in mechanical stress-exposed healthy tissues and its function as a therapy resistance pathway in cancers. We discuss the perspective of targeting this cascade for cancer treatment and weigh its chances and potential risks when considering its emerging role as a protective stress response pathway. KW - atherosclerosis KW - bone KW - cartilage KW - endothelium KW - extracellular-regulated kinase 5 KW - Krüppel-like factor KW - mechanotransduction KW - mitogen-activated protein kinase KW - stress signaling KW - tumor Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-261638 SN - 1422-0067 VL - 22 IS - 14 ER - TY - JOUR A1 - Sian-Hulsmann, Jeswinder A1 - Riederer, Peter T1 - The nigral coup in Parkinson's Disease by α-synuclein and its associated rebels JF - Cells N2 - The risk of Parkinson's disease increases with age. However, the etiology of the illness remains obscure. It appears highly likely that the neurodegenerative processes involve an array of elements that influence each other. In addition, genetic, endogenous, or exogenous toxins need to be considered as viable partners to the cellular degeneration. There is compelling evidence that indicate the key involvement of modified α-synuclein (Lewy bodies) at the very core of the pathogenesis of the disease. The accumulation of misfolded α-synuclein may be a consequence of some genetic defect or/and a failure of the protein clearance system. Importantly, α-synuclein pathology appears to be a common denominator for many cellular deleterious events such as oxidative stress, mitochondrial dysfunction, dopamine synaptic dysregulation, iron dyshomeostasis, and neuroinflammation. These factors probably employ a common apoptotic/or autophagic route in the final stages to execute cell death. The misfolded α-synuclein inclusions skillfully trigger or navigate these processes and thus amplify the dopamine neuron fatalities. Although the process of neuroinflammation may represent a secondary event, nevertheless, it executes a fundamental role in neurodegeneration. Some viral infections produce parkinsonism and exhibit similar characteristic neuropathological changes such as a modest brain dopamine deficit and α-synuclein pathology. Thus, viral infections may heighten the risk of developing PD. Alternatively, α-synuclein pathology may induce a dysfunctional immune system. Thus, sporadic Parkinson's disease is caused by multifactorial trigger factors and metabolic disturbances, which need to be considered for the development of potential drugs in the disorder. KW - Parkinson's disease KW - substantia nigra KW - alpha-synuclein KW - genetics KW - iron KW - neuroinflammation KW - viruses KW - immunology KW - aging and cell death Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-234073 SN - 2073-4409 VL - 10 IS - 3 ER - TY - JOUR A1 - Meir, Michael A1 - Maurus, Katja A1 - Kuper, Jochen A1 - Hankir, Mohammed A1 - Wardelmann, Eva A1 - Rosenwald, Andreas A1 - Germer, Christoph-Thomas A1 - Wiegering, Armin T1 - The novel KIT exon 11 germline mutation K558N is associated with gastrointestinal stromal tumor, mastocytosis, and seminoma development JF - Genes, Chromosomes & Cancer N2 - Familial gastrointestinal stromal tumors (GIST) are dominant genetic disorders that are caused by germline mutations of the type III receptor tyrosine kinase KIT. While sporadic mutations are frequently found in mastocytosis and GISTs, germline mutations of KIT have only been described in 39 families until now. We detected a novel germline mutation of KIT in exon 11 (p.Lys-558-Asn; K558N) in a patient from a kindred with several GISTs harboring different secondary somatic KIT mutations. Structural analysis suggests that the primary germline mutation alone is not sufficient to release the autoinhibitory region of KIT located in the transmembrane domain. Instead, the KIT kinase module becomes constitutively activated when K558N combines with different secondary somatic mutations. The identical germline mutation in combination with an additional somatic KIT mutation was detected in a second patient of the kindred with seminoma while a third patient within the family had a cutaneous mastocytosis. These findings suggest that the K558N mutation interferes with the juxtamembranous part of KIT, since seminoma and mastocystosis are usually not associated with exon 11 mutations. KW - germline mutation KW - GIST KW - KIT KW - mastocytosis KW - seminoma Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-257476 VL - 60 IS - 12 ER - TY - JOUR A1 - Bakari-Soale, Majeed A1 - Ikenga, Nonso Josephat A1 - Scheibe, Marion A1 - Butter, Falk A1 - Jones, Nicola G. A1 - Kramer, Susanne A1 - Engstler, Markus T1 - The nucleolar DExD/H protein Hel66 is involved in ribosome biogenesis in Trypanosoma brucei JF - Scientific Reports N2 - The biosynthesis of ribosomes is a complex cellular process involving ribosomal RNA, ribosomal proteins and several further trans-acting factors. DExD/H box proteins constitute the largest family of trans-acting protein factors involved in this process. Several members of this protein family have been directly implicated in ribosome biogenesis in yeast. In trypanosomes, ribosome biogenesis differs in several features from the process described in yeast. Here, we have identified the DExD/H box helicase Hel66 as being involved in ribosome biogenesis. The protein is unique to Kinetoplastida, localises to the nucleolus and its depletion via RNAi caused a severe growth defect. Loss of the protein resulted in a decrease of global translation and accumulation of rRNA processing intermediates for both the small and large ribosomal subunits. Only a few factors involved in trypanosome rRNA biogenesis have been described so far and our findings contribute to gaining a more comprehensive picture of this essential process. KW - infection KW - parasite evolution KW - parasite genetics KW - RNA Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-263872 VL - 11 IS - 1 ER - TY - JOUR A1 - Eissler, Cristoph A1 - Werner, Rudolf A. A1 - Arias-Loza, Paula A1 - Nose, Naoko A1 - Chen, Xinyu A1 - Pomper, Martin G. A1 - Rowe, Steven P. A1 - Lapa, Constantin A1 - Buck, Andreas K. A1 - Higuchi, Takahiro T1 - The number of frames on ECG-gated \(^{18}\)F-FDG small animal PET has a significant impact on LV systolic and diastolic functional parameters JF - Molecular Imaging N2 - Objectives. This study is aimed at investigating the impact of frame numbers in preclinical electrocardiogram- (ECG-) gated \(^{18}\)F-fluorodeoxyglucose (\(^{18}\)F-FDG) positron emission tomography (PET) on systolic and diastolic left ventricular (LV) parameters in rats. Methods. \(^{18}\)F-FDG PET imaging using a dedicated small animal PET system with list mode data acquisition and continuous ECG recording was performed in diabetic and control rats. The list-mode data was sorted and reconstructed with different numbers of frames (4, 8, 12, and 16) per cardiac cycle into tomographic images. Using an automatic ventricular edge detection software, left ventricular (LV) functional parameters, including ejection fraction (EF), end-diastolic (EDV), and end-systolic volume (ESV), were calculated. Diastolic variables (time to peak filling (TPF), first third mean filling rate (1/3 FR), and peak filling rate (PFR)) were also assessed. Results. Significant differences in multiple parameters were observed among the reconstructions with different frames per cardiac cycle. EDV significantly increased by numbers of frames (353.8 & PLUSMN; 57.7 mu l*, 380.8 & PLUSMN; 57.2 mu l*, 398.0 & PLUSMN; 63.1 mu l*, and 444.8 & PLUSMN; 75.3 mu l at 4, 8, 12, and 16 frames, respectively; *P < 0.0001 vs. 16 frames), while systolic (EF) and diastolic (TPF, 1/3 FR and PFR) parameters were not significantly different between 12 and 16 frames. In addition, significant differences between diabetic and control animals in 1/3 FR and PFR in 16 frames per cardiac cycle were observed (P < 0.005), but not for 4, 8, and 12 frames. Conclusions. Using ECG-gated PET in rats, measurements of cardiac function are significantly affected by the frames per cardiac cycle. Therefore, if you are going to compare those functional parameters, a consistent number of frames should be used. KW - Myocardial-perfusion SPECT KW - left-ventricular function KW - ejection fraction KW - MRI Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-265778 VL - 2021 ER -