Die Funktion neutrophiler Granulozyten im Aszites von Patienten mit dekompensierter Leberzirrhose ist signifikant vermindert, jedoch reversibel nach Inkubation mit autologem Patientenplasma

Patienten mit einer dekompensierten Leberzirrhose besitzen ein hohes Risiko bakterielle Infektionen zu entwickeln. Besonders häufig kommt es dabei zu einer spontan bakteriellen Peritonitis, wobei die Letalität bis heute noch immer bei bis zu 50 % liegt. Ein wesentlicher Grund für das generelle Infektionsrisiko besteht in der Zirrhose-assoziierten systemischen Immunparalyse als Folge einer andauernden Immunstimulation. Es ist allerdings ungeklärt warum bei Patienten mit Leberzirrhose die SBP die häufigste Infektion ist, wohingegen Patienten mit malignem Aszites dafür nicht empfänglich sind. Daher war das Ziel dieser Arbeit, die Funktionseinschränkung von PMNs im Aszites von Patienten mit Leberzirrhose zu evaluieren und dafür die Fähigkeit zur Phagozytose und stimuliertem oxidativen Burst in Aszites- und korrespondierenden Blutproben zu untersuchen

Women’s Internalization of Sexism: Predictors and Antidotes

Not only men, but also many women take an active part in maintaining the current gender system by “doing gender” and by endorsing sexist beliefs. Recent research has identified several psychological factors as predictors of women’s acceptance of sexist attitudes, but a coherent parsimonious theoretical model was still missing. Accordingly, the first purpose of the present research (Manuscript #1) was to shed light on the seemingly paradoxical phenomenon that, even though women belong to the target group of gender discrimination, many of them support the gender hegemony. Based on Social Identity Theory (Tajfel & Turner, 1979) and Social Role Theory (Eagly & Wood, 1999), the Gender Identity Model was developed to explain this phenomenon. Results of a correlational study and two experiments provided clear evidence for the usefulness of the Gender Identity Model to explain differences in women’s endorsement of subtle sexist beliefs and engagement in collective action: Women reject Benevolent, Hostile and Modern Sexism and participate in collective action in particular when they are highly identified with the category women and have, at the same time, internalized progressive identity contents. In contrast, gender role preference has weaker or no effects on sexist beliefs and willingness to engage in collective action when women are low identified with their gender in-group. As a direct consequence of advancing knowledge about predictors to explain endorsement of sexist beliefs, the second part of the present research focused on ways to reduce endorsement of these beliefs (Manuscript #2). So far, no research work has yet investigated a method to reduce subtle sexist beliefs, and only little research has so far analyzed changes in other gender-related concepts which were caused by long-term teaching projects. The second part of the present dissertation (Manuscript #2) therefore aimed at identifying factors which help to reduce subtle sexist beliefs. It was posited that many individuals lack awareness of the prevalence of sexism and the harm experienced by the targets of gender discrimination. A heightened knowledge about the prevalence of sexism was predicted to reduce endorsement of modern sexist beliefs, whereas a heightened sensitivity for the harm of sexism was predicted to result in decreased endorsement of benevolent sexist beliefs. These effects were predicted to be moderated by gender identification. Results of three experimental studies provided strong support for the reduction of prejudice through heightened knowledge about the prevalence and harm of sexism and partial evidence for the moderating role of gender identification: In the first experiment using a daily diary-method, we demonstrated that attending to sexism in everyday life leads to rejection of modern, neo-, and benevolent sexist beliefs in women. In the second experiment, we showed that a heightened sensitivity towards the prevalence of sexism resulted in rejection of modern sexist beliefs, whereas a heightened sensitivity towards harm experienced by the targets of discrimination resulted in rejection of benevolent sexist beliefs. Findings of the third experiment demonstrated that the prejudice reducing effects of the information were consistently stronger for women who are more identified and men who are less identified with their gender in-group. Across all studies, we found that rejection of sexist beliefs generalized to rejection of system justification beliefs

Surpassing Simple Aggregation: Advanced Strategies for Analyzing Contextual-Level Outcomes in Multilevel Models

This article introduces two advanced analytical strategies for analyzing contextual-level outcomes in multilevel models: the multilevel SEM and the two-step approach. Since these strategies are seldom used in comparative survey research, we first discuss their methodological and statistical advantages over the more commonly applied approach of group mean aggregation. We then illustrate these advantages in an empirical analysis of the effect of citizens' support for democratic values at the individual level on a contextual-level outcome - the persistence of democracy - drawing on data from the World Values Survey and the Quality of Government project. Whereas we found no significant effect of support for democratic values in the model using simple group mean aggregation, citizens' support for democratic values was a significant predictor of democracies' estimated survival rate when applying latent aggregation in multilevel SEM and the two-step approach. The article corroborates previous concerns with simple aggregation and demonstrates how researchers can improve the validity of their analyses of contextual-level outcomes by using alternative strategies of aggregation

Role of the mitochondrial ATP-dependent Clp protease in mammalian metabolism

Mitochondria are fundamental for cellular metabolism and take center stage in the regulation of systemic energy metabolism. They are origin and target of nutrient intermediates of converging metabolic pathways. Thus, it is essential to maintain mitochondrial homoeostasis. Cells harbor a large set of mitochondrial proteases involved in quality control, including the ATP-dependent Clp protease (CLPP). However, CLPP not only degrades misfolded or damaged proteins, CLPP is also involved in highly regulated proteolytic activities. Many bacterial and mammalian ClpXP substrates have been identified in various metabolic pathways. This study analyzes the role of CLPP in mammalian metabolism using whole body and tissue-specific Clpp knockout mouse models. The ubiquitous loss of CLPP under normal dietary conditions leads to a lean phenotype with enhanced glucose metabolism. The absence of CLPP further facilitates increased energy expenditure in part by WAT browning, despite decreased physical activity. Moreover, CLPP was shown to be involved in fatty acid oxidation by the regulation of its putative substrate VLCAD. In addition, CLPP has a critical role in BAT homeostasis and cold induced thermogenesis. The mild to moderate mitochondrial dysfunction caused by the loss of CLPP in various tissues, induced the expression of the mitokine FGF21. However, using Clpp/Fgf21 double knockout mice, it could be shown that FGF21 is not mediating the metabolic changes observed in CLPP deficient mice. The tissue-specific depletion of CLPP in liver or skeletal muscle and heart revealed a dispensable role for CLPP with regard to whole body metabolism, although tissue restricted mitochondrial dysfunction was present. Finally, ablation of CLPP was demonstrated to protect against HFD induced obesity and insulin resistance. Remarkably, HFD-feeding impaired hepatic mitochondrial translation in the absence of CLPP resulting in decreased complex subunits and decreased supercomplexes levels in an alternate mechanism as previously described for the heart. Thus, mitochondrial CLPP has a critical role in metabolic stress conditions in particular during cold exposure and high fat diet feeding. Therefore, by analyzing CLPP protease function and its link to metabolic stress this study may help to understand pathologies with deregulated Clpp expression

Of profits, transparency, and responsibility:Public views on financing energy system change in Great Britain

Energy transitions in Great Britain (GB) require public engagement and acceptance, but it is not clear how energy system change is to be financed. In this paper we explore public views on responsibility (of the government in Great Britain, energy companies and residents) to pay for costs associated with energy system change and personal acceptance to contribute financially. Five focus groups with 6-9 participants each, were conducted in four locations across GB. Using thematic analysis to examine responsibility and the role of trust we identified three themes relating to 1) views on profits, 2) lack of transparency and 3) the perceived problematic relationship between energy companies and government. Participants assigned greater responsibility to institutional actors and did not believe that these actors were currently contributing sufficiently. Although participants were prepared to accept some additional costs because they were in favour of energy transitions, they also expressed distrust towards the other actors due to concerns over the profit driven energy system, lack of transparency and perceived close connections between the energy industry and government. These concerns could result in reduced public support for transitions if they remain unaddressed; they highlight a demand for a more equal distribution of costs and benefits and fairer processes in the energy system and transitions

Metasomatized lithospheric mantle for Mesozoic giant gold deposits in the North China craton

The origin of giant lode gold deposits of Mesozoic age in the North China craton (NCC) is enigmatic because high-grade metamorphic ancient crust would be highly depleted in gold. Instead, lithospheric mantle beneath the crust is the likely source of the gold, which may have been anomalously enriched by metasomatic processes. However, the role of gold enrichment and metasomatism in the lithospheric mantle remains unclear. Here, we present comprehensive data on gold and platinum group element contents of mantle xenoliths (n = 28) and basalts (n = 47) representing the temporal evolution of the eastern NCC. The results indicate that extensive mantle metasomatism and hydration introduced some gold (<1–2 ppb) but did not lead to a gold-enriched mantle. However, volatile-rich basalts formed mainly from the metasomatized lithospheric mantle display noticeably elevated gold contents as compared to those from the asthenosphere. Combined with the significant inheritance of mantle-derived volatiles in auriferous fluids of ore bodies, the new data reveal that the mechanism for the formation of the lode gold deposits was related to the volatile-rich components that accumulated during metasomatism and facilitated the release of gold during extensional craton destruction and mantle melting. Gold-bearing, hydrous magmas ascended rapidly along translithospheric fault zones and evolved auriferous fluids to form the giant deposits in the crust

Transport Activity of the Sodium Bicarbonate Cotransporter NBCe1 Is Enhanced by Different Isoforms of Carbonic Anhydrase

Transport metabolons have been discussed between carbonic anhydrase II (CAII) and several membrane transporters. We have now studied different CA isoforms, expressed in Xenopus oocytes alone and together with the electrogenic sodium bicarbonate cotransporter 1 (NBCe1), to determine their catalytic activity and their ability to enhance NBCe1 transport activity. pH measurements in intact oocytes indicated similar activity of CAI, CAII and CAIII, while in vitro CAIII had no measurable activity and CAI only 30% of the activity of CAII. All three CA isoforms increased transport activity of NBCe1, as measured by the transport current and the rate of intracellular sodium rise in oocytes. Two CAII mutants, altered in their intramolecular proton pathway, CAII-H64A and CAII-Y7F, showed significant catalytic activity and also enhanced NBCe1 transport activity. The effect of CAI, CAII, and CAII mutants on NBCe1 activity could be reversed by blocking CA activity with ethoxyzolamide (EZA, 10 µM), while the effect of the less EZA-sensitive CAIII was not reversed. Our results indicate that different CA isoforms and mutants, even if they show little enzymatic activity in vitro, may display significant catalytic activity in intact cells, and that the ability of CA to enhance NBCe1 transport appears to depend primarily on its catalytic activity