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Wahrheitsbindung und Kompromiss : Strategien der katholische Kirche in politisch-ethischen Konfliktthemen
Get PDFWertekonflikte unterschiedlicher Weltanschauungen kennzeichnen die moderne plurale Gesellschaft und stellen Demokratien, die auf Kompromisse angewiesen sind, vor erhebliche Herausforderungen. Religiöse Gemeinschaften, die sich einer ihnen vorausgehenden Wahrheit verpflichtet wissen, wie die katholische Kirche, gelten als kompromissunfähig. Die Fallstudie erörtert anhand des Schwangerschaftsabbruchs, wie die katholische Kirche auch in ethisch schwierigen Themen zu Kompromissen mit anderen gesellschaftlichen Akteuren gelangt und arbeitet Argumentationstypen heraus
Subcellular control of cAMP microdomain signaling using targeted optogenetics
Get PDFIn cardiomyocytes, cAMP/PKA-dependent phosphorylation of LTCC and RyR2 increases Ca2+ transient and contractile force. Due to the close proximity of both proteins, it is still unclear whether their cAMP/PKA microdomains are functionally separated or cross-talk. To investigate differences in selective phosphorylation, we generated cAMP microdomains at the LTCC and the RyR2 using a novel optogenetic approach that subcellularly targets photo-activated adenylate cyclase from Turneriella parva (TpPAC). TpPAC was targeted together with EYFP or mCitrine to RyR2 by fusion with the high-affinity protein FKBP12.6 and to the LTCC ß-subunit by fusion with a specific nanobody (nb.F3). TpPAC-EYFP was used as a control for global cytosolic cAMP generation. Intact light-dependent cAMP generation by TpPAC fusion proteins was detected in HEK293 cells co-expressing the cAMP-sensitive GloSensor, where blue light increased cAMP levels dose-dependently.
After expression in nCMs, TpPAC-EYFP showed a homogeneous distribution. TpPAC-mCitrine-FKBP12.6 localized near the Z-discs, indicating RyR2 targeting, while nb.F3-TpPAC-EYFP showed cell membrane targeting. However, both targeted TpPACs also exhibited some background cytosolic expression. Brief flashes of blue light induced a transient increase in spontaneous beating rate in all constructs in a light dose-dependent manner. The global production of cAMP in the cytosol or the local production at RyR2 by brief light pulses of 250 ms resulted in a long-lasting, constant plateau (>50 s) of the increased beating rate effect. In contrast, the effect of cAMP generation locally at the LTCC declined after its peak, without a clear plateau, but with a longer-lasting, small effect. Ca2+ imaging of electrically stimulated cardiomyocytes (0.75-1 Hz) with the red-shifted dye Cal630 revealed a light-induced increase in the Ca2+ transient height with all three constructs. Interestingly, the local generation of cAMP at RyR2 increased diastolic Ca2+ levels, incontrast to local LTCC or global cAMP generation. Furthermore, PKA phosphorylation intensity analysis showed that TpPAC-mCitrine-FKBP12.6 had already reached 85% of its maximum at low illumination protocols. In contrast, TpPAC-EYFP reached only 45% and TpPAC-nb.F3 43% of its maximum, indicating a higher phosphorylation sensitivity of the RyR2 to low light in response to cAMP generation.
The kinetic differences suggest the light-induced generation of a "large" cAMP pool in the cytosol and RyR2 microdomain and a high PDE expression or activation of a feedback mechanism in the LTCC microdomain. Furthermore, the higher increase of diastolic Ca2+ by cAMP in RyR2 microdomains highlights the significance of PKA-dependent Ca2+ leak from the SR. Hereby, the higher sensitivity to low cAMP increase may be an important mechanism in developing cardiac arrhythmias. In a second preliminary approach, both globally and locally, the inhibition of PKA with the optogenetic LOV-PKI protein was analyzed. A decrease in beating rate and phosphorylation levels was observed upon illumination. This presents another novel tool for the further investigation into the intricate regulatory mechanisms of cAMP microdomains
»Ist in Ordnung, wenn der Pastor mit mir zusammenkommt, um mich zum Christentum zu bekehren, wunderbar« : Mission in interreligiösen Kontaktzonen
Get PDFMission ist in der Religionsforschung ein sensibles Thema. Mission kann Spannungen verursachen und wird mit Kolonialismus in Verbindung gebracht. Meine Forschung beleuchtet, wie unterschiedliche Begriffe und Konzepte von Mission in fünf verschiedenen interkulturell-christlichen Gemeinden in vier Kontexten genutzt werden. Die empirische Herangehensweise bietet neue Einsichten und ergänzt den bestehenden Diskurs über religiöse Diversität, Mission und Dialog. In den untersuchten Kontaktzonen
zeigt sich Mission in drei Dimensionen: persönliches Bezeugen, praktische Liebe und Selbstwerbung. Insgesamt verstehen die im Kontakt stehenden christlichen und muslimischen Gemeinschaften Mission
als eine Form der Beziehungspflege, des öffentlichen Bekenntnisses und der Grenzüberschreitung, die Religion als mehr als eine Privatangelegenheit darstellt.»It’s Fine if the Pastor Joins Me to Convert Me to Christianity – Wonderful« : Mission in Interreligious Contact Zones
In religious research, mission is a sensitive topic. Mission can lead to tensions and is often associated with colonialism. My research sheds light on how different terms and concepts are used in five intercultural Christian communities in four contexts, and how they can enhance a peaceful interreligious coexistence or how they can cause conflicts. The empirical approach offers new insights and complements the existing discourse on religious diversity, mission and dialogue. In the contact zones studied, mission appears in three dimensions: personal witness, practical love and self-promotion. Overall, the Christian and Muslim communities in contact understand mission as a form of relationship-building, public confession and boundary-crossing that presents religion as something more than a private matter.La misión es un tema delicado en la investigación religiosa. La misión puede provocar tensiones y se asocia con el colonialismo. Mi investigación arroja luz sobre cómo se utilizan los distintos términos y conceptos de misión en cinco comunidades cristianas interculturales diferentes de cuatro contextos, y cómo pueden contribuir a una coexistencia interreligiosa pacífica o causar conflictos. El enfoque empírico ofrece nuevas perspectivas y complementa el discurso existente sobre diversidad religiosa, misión y diálogo. En las zonas de contacto analizadas, la misión se manifiesta en tres dimensiones: testimonio personal, amor práctico y autopromoción. En general, las comunidades cristianas y musulmanas en contacto entienden la misión como una forma de construcción de relaciones, confesión pública y traspaso de fronteras que presenta la religión como algo más que un asunto privado
Beyond Pathology: Bringing the Ecological-Enactive Model of Disability to Neuroethics and Mental Health Conditions
Get PDFDesign and development of probes for studying cannabinoid and related orphan G protein-coupled receptors and their signaling
No full textG protein-coupled receptors (GPCRs) are the largest family of human membrane proteins and represent one of the most important classes of pharmacological targets for drugs. Among these, the cannabinoid (CB)receptor subtypes CB1 and CB2 have emerged as attractive targets due to their roles in various pathophysiological processes. Growing evidence indicates that cannabinoids can additionally interact with other GPCRs beyond CB1 and CB2 receptors, in particular with the orphan receptors GPR18 and GPR55. Both receptors have potential as drug targets, but conflicting findings have presented significant challenges in their validation for therapeutic application.
The present study aimed to design, synthesize, evaluate, and characterize tool compounds, for GPR18, CB1 and CB2 receptors. Through screening campaigns, structure–activity relationship (SAR) analysis, and broad pharmacological evaluation, several potent and reliable tools were developed.
For GPR18, the initial hit compounds PSB-KD107 (EC50 = 0.562 µM) and PSB-KD477 (EC50 = 0.454 µM) were used as starting points to yield more potent and selective agonists, including PSB-KK1415 (EC50 = 0.0191 µM), PSB-KK1445 (EC50 = 0.0454 µM), and PSB-KK1418 (EC50 = 0.0711 µM). These compounds present the most potent (PSB-KK1415), most selective (PSB-KK1445) and most efficacious (PSB-KK1418) GPR18 agonists known to date. Additionally, PSB-KK1846 was identified as the most potent antagonist for GPR55, with an IC50 of 0.884 µM. The new agonists were found to display minimal species differences. In contrast, Δ9-tetrahydrocannabinol (THC) – a standard tool compound for this receptor, acted as a weak partial agonist at the mouse GPR18 receptor, and therefore cannot be used for mouse studies of GPR18.
For CB2 receptors, a fluorinated indole derivative, demonstrated high selectivity over other CB and CB-like receptors and exhibited a favorable profile in metabolic stability assays, making it a promising candidate for radiotracer development for positron emission tomography (PET). Diindolylmethane (DIM) and its derivatives were optimized to generate tool compounds for CB2 receptors with distinct pharmacological properties. PSB-19837 (EC50 = 0.0144 µM) was identified as the most potent CB2 agonist in the present series. PSB-19571 exhibited biased agonism toward β-arrestin (6-fold preference for β-arrestin-2 over G-protein signaling), while PSB-18691 showed a Gai-protein bias (20-fold preference for G-protein over β-arrestin-2 signaling).
A further study focused on the adenosine A2A receptor, presenting the crystal structure of the receptor bound to the partial agonist LUF5834, with an atomic resolution of 2.3 Å. Structural studies revealed previously unobserved binding interactions, including the interaction of the phenolic group of LUF5834 with transmembrane helix III, and an ionic lock between the extracellular loops. Pharmacological studies confirmed that LUF5834 acts as a partial agonist, likely stabilizing an equilibrium between active and inactive receptor states.
In conclusion, the present work identified, optimized and broadly characterized small molecules that serve as potent tool compounds for GPR18 and CB2 receptors. In addition, structural and pharmacological studies on the adenosine A2A receptor provided valuable insights into the mechanism of partial agonism at this prototypic GPCR
Metabolic Network Reconstruction of Algal Strains of <em>Chlorella species</em>
Get PDFChlorella is a photosynthetic, eukaryotic microalgae that has received profound interest as a prospective feed source for the production of biofuels. For efficient biotechnological application, the high light tolerance and thereby accelerated growth of some species is of special interest. To uncover the genetic basis of high light tolerance, genome metabolic network reconstruction of high light sensitive and tolerant strains was performed.
For this thesis research work, four Chlorella strains are used for a comparative analysis. Three strains were high light tolerant while one was high light sensitive. The genomes of these algal strains were annotated with gene ontology terms and EC numbers by using InterProScan, InterPro2GO and EC2GO mapping.
With Arabidopsis thaliana as reference genome, ortholog prediction was conducted by using OrthoMCL. BLASTP was used for sequence similarity analysis, whereas for pathway mapping KEGG Pathways mapping tool was used.
Pathway coverage of shared and strain-specific genes was analysed. The results show that in the Oxidative Phosphorylation pathway there is a missing gene in the sensitive strain (Cv11b). This gene belongs to NADH dehydrogenase, Complex-I and functions in the transfer of electrons from NADH to the respiratory chain, while it is present in tolerant strains. The glycerophospholipid metabolism pathway also shows a missing enzyme, PSD3, in the sensitive strain (Cv11b). This gene is present in all tolerant strains. Subsequently, synteny analysis was conducted for the PSD genomic region. The alignment of Cv264 and Cv11b algal strains showed that PSD3-neighbouring genes were located on contig node-207 of the sensitive algal strain Cv11b, however flanking genes to one side of the expected PSD3 location were found in reverse order and orientation in Cv11b. However, the PSD3 gene itself could not be mapped to the Cv11b genome sequence. This indicates that the genomic region of PSD3 is sequenced and assembled in Cv11b, however the PSD3 gene has presumably been deleted.
These differences in metabolic networks could be candidates for further studies regarding their potential to enhance lipid production by using metabolic engineering. Especially PSD3 appears to be an interesting target for high light tolerance as it may be linked to lipid production and the capacity of membranes to maintain function under high light stress
Delirinzidenz an einem Maximalversorger vor und nach Einführung eines intraoperativen EEG-Monitorings
Get PDFPostoperatives Delir ist eine schwerwiegende Erkrankung, die sich auszeichnet durch einen akuten Beginn und fluktuierender Verlauf, Veränderungen der Orientierung zur Person, Aufmerksamkeitsstörung, Bewusstseinsstörung und/oder kognitiv emotionale Störungen wie Erinnerungsverlust oder Sprachstörung. Das Auftreten ist multifaktoriell durch prädisponierende sowie auslösende Faktoren bedingt. Ein Ansatz der Delirprävention bietet intraoperatives EEG-Monitoring. Studien zeigen, dass eine Steuerung der Narkosetiefe anhand dieses Monitorings zu geringerer Delirinzidenz führt.
Die vorliegende Arbeit untersuchte die Delirinzidenz an einem Maximalversorger vor und nach Einführung eines intraoperativen EEG-Monitorings. Von August 2019 bis August 2021 wurden an einem Dortmunder Krankenhaus 1261 Patient*innen mit Alter > 60 Jahre, die sich einer elektiven Operation unterzogen, in die Studie eingeschlossen. In einer Kontroll- (n = 632) und einer Interventionsgruppe (n = 629) wurden bis fünf Tage postoperativ tägliche Visiten durchgeführt und mit den Testscores CAM-ICU oder NuDESC und ICDSC das Vorliegen von POD evaluiert. In der Interventionsgruppe wurde intraoperativ BIS-Monitoring durchgeführt und die Narkoseführung an Zielwerten von 40 bis 60 orientiert.
Die Delirinzidenz lag bei 10,5 % in der Gesamtgruppe. In der Kontrollgruppe trat POD bei 11,1 % der Patient*innen auf, in der Interventionsgruppe lag die Inzidenz bei 9,9 %, entsprechend einer relativen Reduktion von 10,8 %. Unter Männern trat häufiger POD auf als unter Frauen. Im Alter > 80 Jahre trat POD am häufigsten auf, BIS-Monitoring zeigte hier keinen Effekt. Unter ASA IV – klassifizierten Patient*innen war POD am häufigsten. Im orthopädischen Patient*innenkollektiv erzielte BIS-Monitoring den größten positiven Effekt und eine relative Reduktion der Delirrate um 50 %. Nach herzchirurgischen OP-Prozeduren trat am häufigsten POD auf, in der Interventionsgruppe häufiger als in der Kontrollgruppe (27,2 % versus 25,7 %). BIS-Monitoring zeigte keinen signifikanten Effekt auf das Auftreten von POD. Es zeigte sich aber unter allen OP-Prozeduren, ausgenommen herzchirurgisch, ein positiver Effekt von BIS-Monitoring erkennbar an geringeren POD-Raten in den Interventionsgruppen.
POD kann am effektivsten vorgebeugt und behandelt werden im Rahmen von interdisziplinären und individuellen Evaluationen und Interventionen. Intraoperatives EEG-Monitoring und einhergehende Steuerung von Narkosetiefe bietet einen Ansatzpunkt in der Vermeidung von POD, und führt gleichzeitig zu keinem beobachteten Schaden oder unerwünschten Nebenwirkungen. Es sollte standardisiert von geschultem Personal zur Narkosesteuerung hinzugezogen werden, weitere Studien und Analysen zur Unterstützung und Differenzierung dieser Aussage sind sinnvoll
Effects of using the internet on smallholder farmers’ income and dietary quality in Bangladesh
Get PDFThe internet is expanding at a rapid rate, which is true even in rural areas of low- and middle-income countries. The internet affects how people produce and consume food and other goods and services. This may also have implications for incomes and diets in smallholder farm households, where poverty and undernourishment are still commonplace. Here, we use primary data collected from 720 farm households in Bangladesh to analyze how using the internet affects agricultural production activities and food consumption choices. Potential issues of endogeneity are addressed through an instrumental variable approach and other quasi-experimental methods. Our results suggest that using the internet increases farm production diversity, commercialization, and income by improving farmers’ access to markets, information, and innovative ideas. We also find positive effects on dietary diversity, even though the results depend on the concrete dietary indicators used. Strikingly, using the internet seems to encourage the production of certain nutritious and profitable foods but does not always lead to an increase in their consumption. Our results highlight the important role of the internet in enhancing farm productivity, income, and potentially also diets. At the same time, our findings also suggest that more efforts are needed to improve dietary outcomes and nutrition
Amtliche Bekanntmachungen, 55. Jahrgang, Nr. 69
No full textOrdnung zur Änderung der Prüfungsordnung für den Bachelorstudiengang „Psychologie“, den konsekutiven Masterstudiengang „Psychologie“ und den konsekutiven Masterstudiengang „Psychologie mit Schwerpunkt Klinische Psychologie und Psychotherapie“ der Philosophischen Fakultät der Rheinischen Friedrich-Wilhelms-Universität Bonn vom 18. August 202
The hard work of future-making : Alienated futures, invisible labour and liberation
Get PDFThis article proposes that future-making is hard work. Drawing on examples of work on and around infrastructure projects in East Africa, we show how people orient themselves towards the future through both imagination and material practices. We argue that work navigates between apparent opposites, and identify three antagonisms that are particularly relevant to our argument. First, we discuss how labour mediates between material reality and anticipatory imagination, extending this argument to include a mediation between material present and immaterial future imaginaries. Second, we show how labour can oscillate between visible, even spectacular, performance of labour and employment, and the invisible work of often marginalised people. Finally, we argue that while labour is often characterised by exploitative dynamics, it also offers possibilities for resistance – as well as promises of liberation – through organised labour in various forms. We conclude that (organised) labour, particularly around infrastructure projects, has the potential to make marginalised futures visible and real, thus challenging dominant imaginaries and material realities of the future inscribed by infrastructure master plans. These arguments are illustrated by vignettes collected during fieldwork on the Nairobi Express, along the proposed Lamu Port-South Sudan-Ethiopia-Transport (LAPSSET) corridor in Kenya and around a dam construction site in Tanzania