Identity Performance in British Rock and Indie Music : Authenticity, Stylization, and Glocalization

This master’s thesis, departing from the work done by Peter Trudgill and Paul Simpson, aims at widening the scope of research on the identity performance of British rock and indie musicians by taking into account the influences and intersections of local and global social contexts. It not only analyzes the musicians’ accents but also focuses on their lyrics, music videos and statements in interviews. The different types of data are analyzed for references of place in relation to theories of discourse, stylization and authenticity. The thesis applies the concept of glocalization, which has been widely used in studies of hip hop music, to the genres rock and indie in order to explain how local and global forces influence discursive identity production, particularly in relation to popular culture. The first phase of the study is a lyrical analysis of five British bands. Based on the results of the first phase, three bands were chosen for in-depth multimodal discourse analysis in a second phase. Results show how the bands' identity performances were changed and (re)shaped over the course of their careers. The study reveals three different profiles of the approach to and the development of identity performance, highlighting the importance of individuality in the face of mass media. In all, with respect to methodology, the study illustrates the benefit of discourse-analytic case study for the investigation of identity performance by musical artists

SUMOylierung

Die vorliegende Arbeit untersucht die Frage, ob humanes CFTR-Protein (Cystic Fibrosis Transmembrane Conductance Regulator) sumoyliert wird und welche funktionelle Bedeutung die Sumoylierung des CFTRs hat. In der kaukasischen Bevölkerung gilt die Cystischen Fibrose (CF) oder Mukoviszidose als eine der häufigsten Erbkrankheiten. Mutationen im CFTR-Gen, die zu einer drastischen Beeinträchtigung der Funktion des CFTR-Proteins führen, bilden die molekulare Basis der Entstehung der CF. So sind häufig die Reifung und der Transport von CFTR an die Plasmamembran betroffen. Diese Prozesse und verschiedene Aktivitätszustände im CFTR werden u.a. durch posttranslationale Modifikationen (z.B. Phosphorylierungen) spezifischer Konsensus-Motive reguliert. In diesem Zusammenhang führte eine genaue Betrachtung der Primärsequenz von CFTR zur Identifikation von zwei hoch konservierten Motiven, die dem publizierten SUMO-Konsensus-Motiv (ψKxE, nachfolgend SUMO-Motiv genannt) an Position 447 und 1486, bezogen auf das zentrale Lysin, an welchem die Sumoylierung stattfindet, entsprachen. Die Sumoylierung, als eine Form der posttranslationale Modifikationen, wird durch kleine Ubiquitin-ähnliche Proteine (small ubiquitin-like modifier, SUMO) vermittelt. Diese stellen eine Klasse von regulatorischen Proteinen dar, die die Aktivität des Zielproteins, dessen Lokalisation oder die Interaktion mit anderen Proteinen steuern. Damit ergab sich ein relevanter Anknüpfungspunkt, die Rolle der bislang für die CFTR-Regulation noch nicht beschriebenen Form der posttranslationalen Kontrolle durch Sumoylierung zu untersuchen. Als Resultat der hier beschriebenen Untersuchungen konnte die Sumoylierung als notwendiger Bestandteil der Regulation des intrazellulären Transportes von CFTR identifiziert werden. Konkret wurde mit dem Yeast-Two-Hybrid-Verfahren gezeigt, dass CFTR-Domänen an den identifizierten SUMO-Motiven in der Nukleotid-bindedomäne 1 (NBD-1) und am C-Terminus von CFTR sumoyliert werden. Im Säugerzellsystem wurde die spezifische Sumoylierung kompletten CFTRs durch transiente Transfektion von CFTR- und SUMO-Expressionskonstrukten sowie in Zellen, welche CFTR und SUMO endogen exprimieren, verifiziert. Verhindert man weiterhin auf transiente Weise in Säugerzellen die Sumoylierung, durch Mutation der beiden SUMO-Motive oder durch Überexpression der SUMO-spezifischen Protease (SENP1), erreicht CFTR nicht die apikale Plasmamembran. Im Gegensatz zu F508, welches im ER verbleibt, wird CFTR, welches Mutationen in den SUMO-Motiven trägt, im Golgi-Apparat zurückgehalten. Diese Beobachtung konnte mit Hilfe der Dichtegradientenzentrifugation und anschließendem Nachweis der Proteine in den entsprechenden Fraktionen über die Western-Blot-Methode gezeigt werden. Abschließend wurden am Beispiel eines zum SUMO-Motiv benachbart gelegenen Di-Leucin-Motives erste experimentelle Hinweise erhalten, wonach beide CFTR-Motive in der Interaktion mit dem für den vesikulären Transport funktionell wichtigem Adaptor-Protein (AP) Komplex zusammenwirken. Mit den vorliegenden Resultaten konnte erstmals die Hypothese formuliert werden, dass die hier beschriebene Sumoylierung eine Form der Modifikation ist, welche am Transport von CFTR an die Plasmamembran maßgeblich beteiligt ist

Transport of metal oxide nanoparticles across the human air-blood barrier : interactions with physiologically relevant media and proteins

There is still a big gap between nanoparticle production and industrial use on one hand and the knowledge of their toxicological potential on the other. In vitro assays are a common tool to investigate toxicity of substances, but for nanoparticles, some especially dispersion related pitfalls must be recognized and bypassed prior to correct interpretation of results. One special feature of nanoparticles is the possible interaction with proteins in cell culture media and with physiological proteins as well. On one hand, those interactions can have an influence on the agglomeration state, on the other hand cell reactions and hence the toxicological potential can be altered. Investigations with the model protein BSA or FCS, respectively, revealed differences for the adsorption onto nanoparticles, although the particles tested had very similar physico-chemical properties. BSA seemed to adsorb to the particles in different conformations, and the state of agglomeration must be taken into account to draw conclusions about protein adsorption. Protein adsorption was also confirmed for physiologically relevant Surfactant protein A to eight different nanoparticles of partially the same bulk material. Also here, differences in protein adsorption could be detected. In contrast to BSA, Sp-A does not have much impact on the agglomeration state of the particles. Inhaled particles might cross the air-blood barrier and enter the blood stream. Hence, an in vitro air-blood barrier model was adapted to transport experiments with nanoparticles. The cell culture conditions were adapted and the transport characteristics of the cells confirmed. Except two different CeO2 particles, no metal oxide nanoparticle transport could be detected.Noch immer ist die Schere zwischen der Produktion und großtechnischer Nutzung von Nanopartikeln einerseits und deren toxikologischen Potentials andererseits recht groß. In vitro-Versuche sind ein oft genutztes Mittel zur Bestimmung der Toxizität von Substanzen, für Nanopartikel jedoch müssen in diesem Zusammenhang bestimmte Fallen erkannt und umgangen werden, um so generierte Ergebnisse richtig zu interpretieren. Eine Besonderheit von Nanopartikeln ist deren Interaktion mit Proteinen in Zellkulturmedien, aber auch mit physiologisch relevanten Proteinen. Einerseits können solche Interaktionen einen Einfluss auf den Agglomerationsgrad der Partikel, andererseits auf die Reaktion der Zelle auf einen solchen, mit Proteinen überzogenen Partikel haben. Somit kann sich das toxikologische Potential von Nanopartikeln in beide Richtungen verschieben. Bei Untersuchungen mit dem Modellprotein BSA bzw. FCS konnten Unterschiede in der Adsorption an drei Nanopartikel gleichen Materials als auch sehr ähnlichen physikalisch-chemischen Eigenschaften aufgezeigt werden. Dabei zeigte sich, dass BSA wahrscheinlich in unterschiedlichen Konformationen an die Partikel bindet. Außerdem muss, um Proteinadsorption richtig einschätzen zu können, der Agglomerationsgrad der Partikel mit einbezogen werden. Protein-Adsorption konnte nicht nur für Modellproteine, sondern auch für das physiologisch relevante Surfactant Protein A an acht verschiedene Partikel, teilweise aus gleichem Material, nachgewiesen werden. Im Gegensatz zu BSA hat die Dispersion in Sp-A-haltigem Medium keinen positiven Einfluss auf das Deagglomerationsverhalten der Partikel. Inhalierte Partikel können möglicherweise die Blut-Luft-Schranke passieren und so in den Blutkreislauf gelangen. Um den Partikelübertritt zu untersuchen, wurde ein in vitro Zellkultur-Modell an die Besonderheiten von Transportversuchen mit Nanopartikeln angepasst. Die Zellkultur-Bedingungen wurden angepasst und anschließend die Transporteigenschaften der Zellen mit diesen veränderten Gegebenheiten bestätigt. Mit Ausnahme der beiden getesteten CeO2-Partikel konnte im Rahmen der Versuchsdurchführung bei keinem Nanopartikel ein Transport festgestellt werden

Mitotic degradation of cyclin A is mediated by multiple and novel destruction signals

AbstractExit from mitosis requires Cdk1 inactivation, with the most prominent mechanism of Cdk1 inactivation being proteolysis of mitotic cyclins [1]. In higher eukaryotes this involves sequential destruction of A- and B-type cyclins. CycA is destroyed first, and CycA/Cdk1 inactivation is required for the metaphase-to-anaphase transition [2]. The degradation of CycA is delayed in response to DNA damage but is not prevented when the spindle checkpoint is activated [3, 4]. Cyclin destruction is thought to be mediated by a conserved motif, the destruction box (D box). Like B-type cyclins, A-type cyclins contain putative destruction box sequences in their N termini [5]. However, no detailed in vivo analysis of the sequence requirements for CycA destruction has been described so far. Here we tested several mutations in the CycA coding region for destruction in Drosophila embryos. We show that D box sequences are not essential for mitotic destruction of CycA. Destruction is mediated by at least three different elements that act in an overlapping fashion to mediate its mitotic degradation

Cortisol response to traumatic stress to predict PTSD symptom development – a systematic review and meta-analysis of experimental studies

Background: Pre-and post-traumatic hypothalamic–pituitary–adrenal (HPA) axis markers have been studied to predict posttraumatic stress disorder (PTSD) risk, but its acute reactivity cannot be measured in real-life settings. Experimental paradigms can depict the cortisol response to stimuli that simulate traumatic events. Objective: To review experimental studies on the cortisol response to traumatic stimuli and the correlation between cortisol and PTSD symptoms. Method: Experimental, (un-)published studies in German or English from any year were eligible if they confronted non-traumatized humans with traumatic stimuli, assessed cortisol before, during or after stimulus presentation and subsequent PTSD symptoms. The literature was searched via PubMed, PubPsych, PsychINFO, PsycArticle, Web of Science, EMBASE, ProQuest and ClinicalTrials.gov up to 16th February 2021. Risk of bias was assessed with the Cortisol Assessment List. Multilevel-meta-analyses were conducted under the random effects model. The standardized mean change (dSMC) indicated the cortisol response. Coefficient r indicated the correlations between cortisol and PTSD symptoms. Results: 14 studies, investigating 1004 individuals, were included. A cortisol response was successfully induced between 21 and 40 min post-presentation onset (kobservations = 25, dSMC = 0.15 [.03; .26]). Cortisol was not associated with overall or cluster-level PTSD symptoms. On a symptom-level, higher pre-presentation onset cortisol was correlated with lower state tension (k = 8, r = −.18 [−.35; −.01]), higher state happiness (k = 8, r = −.34 [−.59; −.03], variable inverted) and lower state anger (k = 9, r = −.14 [−.26; −.01]). Higher post-presentation onset cortisol was correlated with higher state happiness (k = 16, r = −.20 [−.33; −.06]) and lower state sadness (k = 17, r = −.16 [−.25; −.05]), whereas cortisol response was positively correlated with state anxiety (k = 9, r = .16 [0.04; 0.27]). Conclusions: Experimental paradigms effectively induce a cortisol response. Higher basal cortisol, higher cortisol, as measured after traumatic stimulus presentation, and a lower cortisol response were associated with more adaptive emotional reactions. These markers did not predict longer-term PTSD symptoms

Plasma proteome correlates of lipid and lipoprotein: biomarkers of metabolic diversity and inflammation in children of rural Nepal.

Proteins involved in lipoprotein metabolism can modulate cardiovascular health. While often measured to assess adult metabolic diseases, little is known about the proteomes of lipoproteins and their relation to metabolic dysregulation and underlying inflammation in undernourished child populations. The objective of this population study was to globally characterize plasma proteins systemically associated with HDL, LDL, and triglycerides in 500 Nepalese children. Abnormal lipid profiles characterized by elevated plasma triglycerides and low HDL-cholesterol (HDL-C) concentrations were common, especially in children with subclinical inflammation. Among 982 proteins analyzed, the relative abundance of 11, 12, and 52 plasma proteins was correlated with LDL-cholesterol (r = -0.43∼0.70), triglycerides (r = -0.39∼0.53), and HDL-C (r = -0.49∼0.79) concentrations, respectively. These proteins included apolipoproteins and numerous unexpected intracellular and extracellular matrix binding proteins, likely originating in hepatic and peripheral tissues. Relative abundance of two-thirds of the HDL proteome varied with inflammation, with acute phase reactants higher by 4∼40%, and proteins involved in HDL biosynthesis, cholesterol efflux, vitamin transport, angiogenesis, and tissue repair lower by 3∼20%. Untargeted plasma proteomics detects comprehensive sets of both known and novel lipoprotein-associated proteins likely reflecting systemic regulation of lipoprotein metabolism and vascular homeostasis. Inflammation-altered distributions of the HDL proteome may be predisposing undernourished populations to early chronic disease

Increased Regional Epicardial Fat Volume Associated with Reversible Myocardial Ischemia in Patients with Suspected Coronary Artery Disease

Epicardial adipose tissue is a source of pro-inflammatory cytokines and has been linked to the development of coronary artery disease. No study has systematically assessed the relationship between local epicardial fat volume (EFV) and myocardial perfusion defects. We analyzed EFV in patients undergoing SPECT myocardial perfusion imaging combined with computed tomography (CT) for attenuation correction. Low-dose CT without contrast was performed in 396 consecutive patients undergoing SPECT imaging for evaluation of coronary artery disease. Regional thickness, cross-sectional areas, and total EFV were assessed. 295 patients had normal myocardial perfusion scans and 101 had abnormal perfusion scans. Mean EFVs in normal, ischemic, and infarcted hearts were 99.8 ± 82.3 cm3, 156.4 ± 121.9 cm3, and 96.3 ± 102.1 cm3, respectively (P < 0.001). Reversible perfusion defects were associated with increased local EFV compared to normal perfusion in the distribution of the right (69.2 ± 51.5 vs 46.6 ± 32.0 cm3; P = 0.03) and left anterior descending coronary artery (87.1 ± 76.4 vs 46.7 ± 40.6 cm3; P = 0.005). Our results demonstrate increased regional epicardial fat in patients with active myocardial ischemia compared to patients with myocardial scar or normal perfusion on nuclear perfusion scans. Our results suggest a potential role for cardiac CT to improve risk stratification in patients with suspected coronary artery disease