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    Talentierte symbiontische Naturstoffproduzenten als Quelle neuer Wirkstoffe

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    Amtliche Bekanntmachungen 50. Jahrgang, Nr. 5

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    Ordnung zur Regelung des Verfahrens zur Auswahl von Weiterbildungsstudierenden für die weiterbildenden Masterstudiengänge „Rechtspsychologie mit dem Schwerpunkt Psychologie im Straf- und Maßregelvollzug“ und „Rechtspsychologie mit dem Schwerpunkt Begutachtung im Straf- und Zivilverfahren“ vom 29. Februar 202

    Mining and small-scale farming in the Andes: Socio-environmental roots of land-use conflict

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    The Peruvian Andes are one of the most important water sources for the country. Therefore, their exploitation might pose critical threats for local farming activities, national economy, and water quantity and quality. At the same time, the Andes have experienced activities of the mining industry over the last decades, which has boosted the national economy. The mining concessions and operations have brought together campesino communities and mining companies. This has led to the escalation of conflicts due to mining impacts on water, the mining-related misinformation, the distribution of mining royalties, and the compensations in return to the rent of campesino community lands to mining companies. Focused on the farming-mining lands, this research adapts mixed-methods to analyze the land-use conflicts and to build a risk index to support decision-making processes. It aims to evaluate the environmental, social and institutional roots of land-use conflicts to model conflicting situations between the small-scale farming communities and mining companies. It follows four key objectives. First, the analysis of heavy metal concentrations in water and soil with land-cover classification and participatory mapping allowed the measurement of key biophysical parameters in farming-mining lands. Second, mixed-methods via semi-structured surveys, in-depth interviews, social and content analyses were used to assess the social and institutional aspects related to the management of water and soil. Third, the results from the multi-criteria analysis were compared with content analysis, surveys and interviews to integrate and consolidate the aforementioned biophysical, social and institutional components in a theoretical framework and land-use conflict risk index. Fourth, three main scenarios were developed to simulate the conflicts between communities and mining companies. The resulting land-use conflict risk index can provide a useful decision-making tool for the governments to tackle conflict management through revealing the conflict-triggering criteria and indicators. Furthermore, this is the first interdisciplinary research that depicts a thorough understanding of the interaction of the fourteen studied campesino communities with state institutions, civil society, and mining companies once the mining concession is given

    The role of diacylglycerol acyltransferase 1 in hepatic medium-chain fatty acid metabolism

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    Fatty acids form a class of important biomolecules, serving as essential elements of lipid molecules. Stored in triacylglycerol (TAG), the main constituent of plant oils and animal fats, they from an inseparable part of the daily human diet. Differing carbon chain length and saturation degrees, lead to a great variety of fatty acids in which long-chain-fatty acids (LCFAs) from the major part. The class of medium-chain fatty acids (MCFAs) are mainly found in a variety of plant oils like palm kernel oil and they possess different biochemical and physiochemical properties then LCFAs. Although the cellular metabolism of MCFAs has been object to research for many decades, it is still insufficiently studied in certain details. This thesis connects to previous work in our laboratory where it was proposed that diacylglycerol acyltransferase 2 (DGAT2) plays predominant role in MCFA-TAG synthesis and that cytosolic MCFA-CoAs for TAG synthesis are provided in a carnitine palmitoyltransferase 1 (CPT1)-dependent manner, as treatment with the CPT1 inhibitor Etomoxir reduced MCFA-TAG levels. This present work puts its emphasis on investigating the hepatic metabolism of DGAT-dependent MCFA incorporation into TAG upon treatment with small molecule inhibitors, targeting either DGAT enzymes or mitochondrial CPT1. Freshly isolated primary hepatocytes from wildtype (WT)- or DGAT1-/--mice were treated with inhibitors and pulsed with alkyne fatty acids, followed by lipid extraction and subsequent analysis of the lipid metabolites via thin layer chromatography or mass spectrometry (MS). Here, a novel MS- based methodology to analyze alkyne labeled lipids which was recently developed in our group, was utilized. As observed with the Etomoxir treatment, it was found that a DGAT1 inhibition in WT hepatocytes resulted as well in a MCFA-TAG reduction. Also, a combination of both inhibitors reduced MCFA-TAG levels even further. A DGAT2-inhibition, however, did not alter MCFA-TAG levels. Further, pulse-chase analysis with unlabeled decanoic acid revealed similar effects upon DGAT1 and Etomoxir treatment. Analysis of the lipid profile in DGAT1-/--mice revealed altered MCFA-TAG levels, independent from inhibitory treatment. Interestingly, in DGAT1-/- hepatocytes, Etomoxir-treatment did lead to a similar change in TAG levels as in the WT control. Additionally, in vivo lipopolysaccharide (LPS)- stimulated mice showed overall enhanced lipid levels, but similar responses to the DGAT inhibitor and Etomoxir treatment. Teglicar, another CPT1 inhibitor, did show enhanced TAG synthesis upon treatment. This thesis was concluded by introducing the hypothesis, that hepatic DGAT1 but not DGAT2 is responsible for MCFA incorporation into TAG, which can be compensated partially by DGAT2. It was postulated, that Etomoxir can also act as a potent DGAT inhibitor, predominantly targeting DGAT1, when both DGATs are present. This putative off target effect was not seen with the second CPT1 inhibitor Teglicar

    Functional Integration of Floral Plant Traits: Shape and Symmetry, Optical Signal, Reward and Reproduction in the Angiosperm Flower

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    Pollination syndromes represent groups of floral phenotypes that have originated and diversified in interaction with biotic and abiotic pollen vectors. Plant trait pattern that constitute respective syndromes have been used extensively to predict pollen vectors. However, research in this field has seemingly suffered from poor data quality and insufficient integration of important traits. Main objective of this dissertation is to contribute to better understanding of floral functional integration. Methods of choice are hierarchical clustering, Nonlinear Multidimensional Scaling and vector fitting, amongst others. The following study groups were selected: In chapter II diversification of floral plant traits and pollinator guilds are presented for members of order Geraniales. The order is small but florally diverse, and therefore particularly suitable for comparative studies. Floral symmetry in this order appears to be uncorrelated to quantitatively assessed gamete production and nectar reward. In chapter III diversification of floral plant traits and flowering time are analysed for Hamamelidaceae, a small family known for the peculiar flowering time of some of its members in late autumn or winter. Clear clusters of anemophilous, zoophilous and ambophilous pollination syndromes are retrieved, uncorrelated to flowering time. In chapter IV floral plant traits of carnivorous active flypaper plants Pinguicula and Drosera are compared. Carnivorous plants are animal pollinated, and the potential capture of legitimate pollinators has long been researched under the term pollinator-prey conflict. Analysis of floral plant traits proves the absence of such a conflict. In chapter V subsets of floral functional traits are analysed for 18 members of Streptocarpus subgenus Streptocarpus. The subsets appear to be largely uncorrelated and show an arbitrary distribution on the phylogenetic tree. Reported flower types of the subgenus, commonly described as indicators for pollination syndromes, only correlate to floral architecture. In chapter VI crossing experiments between three closely related Streptocarpus species of the Cape primrose clade demonstrate vigorous seed set. The experiment proves the absence of postzygotic crossing barriers and supports the theory of a large, single gene pool underlying the subgenus. Prezygotic barriers such as eco-geographical isolation, including control of plant-animal interactions via floral architecture and optical attraction, appear to keep the species separated in the field. In chapter VII a more extensive crossing experiment with nine parental species of Streptocarpus subgenus Streptocarpus is presented. Floral architecture, optical signal and nectar reward of 40 hybrids is presented. Hybrids predominantly show full floral function. Establishment of functional hybrid swarms in the field and onset of homoploid hybrid speciation is therefore possible, if a freak pollination event circumvents established prezygotic crossing barriers.   Chapter VIII presents general conclusions of this thesis. All in all, the quantitative and qualitative, integrative assessment of floral plant traits appears as a promising approach for better understanding of floral function, and is an improvement compared to the widespread assessment of pollination syndromes only based on floral colours and shapes

    The Acyl-ACP Thioesterase FatM from <em>Lotus japonicus</em> is involved in lipid transfer during Arbuscular Mycorrhiza Symbiosis

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    Language choice as a gate-keeping practice : an exploration into the psycho-social impacts of multilingualism through case studies from the educational and judicial sectors of Pakistan

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    Pakistan is a multilingual and multi-ethnic country: all the provinces have their own regional languages as lingua franca, i.e., Punjabi in Punjab, Pashto in Khyber Pakhtunkhwa, etc.; Urdu is the national language, i.e., it is the language of majority of the state schools and of the media; whereas English, owing to its colonial past, is the official language of Pakistan, i.e., it is the language of the official transactions, the constitution, law and higher education in the country. Such division means that individuals may have to switch from one language to another when they move from home to school, to work settings, or to official business in public or private offices. The analysis of the data collected from different sites (educational and judicial sectors) reveals how and why the discourses of differential use of languages, created and shaped by the educational institutes, are affected by the overall linguistic attitudes existing in society towards different languages. This research concludes that, on the societal level, this differential language system excludes those who do not know a particular language, i.e., English, and disempowers them structurally from getting their due share of state-provided services, such as justice and education. In 2013, all the stakeholders working for the development of Pakistan, both public and private, came together and agreed upon an agenda for development, called Vision 2025. This document is an aspirational tool to be used as a conceptual framework for steering the country into the direction of sustainable and inclusive development. The aim of this vision is to bring Pakistan among the top 25 world economies by year 2025. In order to see whether such ambitious attempts, as outlined in the document, complement or contradict the already existing social realities and discourses of development remains central theme to the current research. In this regard, language policies, perceptions, attitudes, and daily practices become the lens that is used to investigate the relation between the theoretical aspirations and practical situations on the ground. Language choice becomes a contested field in a multilingual society. Any act of speech in such societies is a political act, where different languages are chosen for different purposes. In a contemporary globalized world where one language, i.e., English enjoys the most acceptance; those who know better English acquire added leverage and symbolic power over others in everyday interactions of members of Pakistani society. This dissertation maintains that fascination with English in the context of Pakistan is actually a colonial legacy that has worked towards establishing and perpetuating symbolic superiority against other languages and speakers of those languages in contemporary Pakistani society. My contribution departs from the traditional themes of political economy of nation-state models that focus on the broader themes of nation-building and the issues of governance, identity and marginality in a post-colonial nation(s). I attempt to address the questions of power and distribution of linguistic resources in Pakistani polity from a sociological angle. In the following pages, I specifically conceptualise and analyse the social practices, attitudes and discourses of marginality and identity construction along linguistic lines by using the concepts of habitus, field, capital, and symbolic power. This dissertation tries to untangle multilingualism from two broad themes: 1) it addresses the questions of the sociocultural dominance of English and Urdu languages over regional languages; 2) it shows how the distribution of linguistic resources is contested, negotiated and reproduced in the praxis of the stakeholders interacting in a multilingual setting. In order to conduct an empirical investigation, two sectors are selected, i.e., the educational and judicial sectors of Pakistan. The rationale behind this choice is both theoretical and practical. The educational sector is selected as it becomes the seedbed where discourses and perceptions are produced and reproduced for the official and legitimate practices of language use; whereas, the judicial sector is selected as it links directly with the manifestation of these discourses and perceptions. It is in the judicial sector, where one sees the direct effects of knowing or not knowing a specific language manifested as every letter, word, and comma, matters in the judicial proceedings. An institute that is responsible for disseminating justice to the citizens of the state, the judicial system uses a language (English) that is alien to the majority of Pakistani population. For example, only in the Punjab province, around 45% of the total population speaks Punjabi, whereas only 4-7% can speak or understand English, yet the judicial system in its official discourse conducts all its business in English. The laws, court proceedings, and verdicts disseminated in various trials in the judicial courts are conducted in English. This research aims at finding out whether this very act of conducting judicial proceedings in English disenfranchises the masses from the system. A mixed-method research design was used to investigate these questions at the public universities and judicial courts in Pakistan. The question remains if and how the choice of language in education can become a tool for estrangement and exclusion. Discourses of development and language-based inequality seem to exist next to each other, weaved seamlessly in the overall social fabric, habitus, of the contemporary Pakistani society. The empirical evidence from the educational institutes further elaborates why a certain language, e.g., English, is preferred at the expense of others. What kind of benefits and disadvantages are entailed in knowing or not knowing English and what kind of identities are associated with English and other languages, such as Punjabi. The underlying generative principle, habitus, combines this language-based inequality with development in a way that current education policy actually perpetuates ideologies, perceptions and practices of social inequalities. These structurally inculcated distinctive principles inadvertently “convince” the dominated, the less-advantaged, into accepting the conditions of his/her own dominance as natural, thereby resulting in symbolic constraint. Moreover, this research shows how language is used as an aspirational capacity for social mobility and what hurdles, both social and psychological, students face in using this capacity in their prospective lives. Historically speaking, after the independence of Pakistan, the British rulers left in 1947, but the unequal social spaces they created stayed behind as these arrangements suited those who were already working under the British rule. Under such conditions and neo-colonial patterns of life, there emerges a hybrid form of speech; one where words of Urdu, English, Punjabi or other regional languages are inter-mixed. An act of using a signifier of one language, say English, while speaking in another language, say Urdu or Punjabi, results in providing extra leverage, symbolic superiority, and authority to the speaker. This hybrid speech serves two purposes; a) it keeps the power inequality intact as it renders one language, i.e., English, superior over all other local languages, and b) it helps to appease those who, not having the capacity to compete in the English dominant market, nevertheless remain at the periphery of the circle, trying to carve out their own spaces. Thus the linguistic interactions, eventually and inadvertently, result in shaping, reproducing, and reinforcing the sociological habitus that in the first place creates social inequalities generated by varied use of languages for various purposes. Therefore, it is argued that the official discourse of sustainable development, though promising in principle, stands miles away from the social realities of development of Pakistan. The development experts, both national and international, have to consider the socially participative model of development in order to address the pressing challenges of nation-building as compared to state-building as far as the language related problems of the Pakistani society are concerned

    The enzyme HPGD is critical for regulatory T cell function in adipose tissue

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    Regulatory T cells (Treg cells) are essential for maintaining immune homeostasis. However, how Treg cells exert their function in tissue specific environments is often unknown. We have found hydroxyprostaglandin dehydrogenase (Hpgd), the major Prostaglandin E2 (PGE2) metabolizing enzyme, to be significantly upregulated in Treg cells compared to conventional T cells (Tconv). In the murine system, this upregulation is especially pronounced in the visceral adipose tissue (VAT), a prostaglandin-rich environment. Furthermore, we could show that through the metabolism of PGE2 into 15-keto-PGE2 Hpgd enhances the suppressive capabilities of Treg cells in an, at least partially, Pparγ-dependent manner. In vivo, we found that Hpgd-deficient Treg cells were less efficient in preventing the onset of both DSS-induced and adoptive transfer colitis, further indicating that Hpgd plays a role in the suppressive capacity of Treg cells. However, analysis of the transcriptome of these Hpgd-deficient Treg cells did not differ significantly from Hpgd-competent Treg cells, indicating that the observed changes are due to the extrinsic effect caused by the loss of the enzymatic function of Hpgd. When analyzing the VAT of aged animals with Hpgd-deficient Treg cells, we could detect an influx of non-functional Treg cells as well as an accumulation of pro-inflammatory macrophages and an increase in adipocyte size. Furthermore, while we could neither detect a change in body or organ weight of these animals, nor a change in motility, food and water intake, or respiration, we could observe impaired metabolic signaling. Aged animals with Hpgd-deficient Treg cells respond less to insulin and glucose challenge and show a reduction in insulin signaling. When subjecting animals with Hpgd-deficient Treg cells to a high fat diet (HFD), we could not detect a difference in weight gain when compared to wildtype littermate control animals. Even though we could detect a slight decrease in insulin responsiveness in animals on a HFD with Hpgd-deficient Treg cells, no difference in the VAT-resident immune cell population or in any other metabolic parameters could be observed. Additionally, in peripheral blood from human type II diabetes (T2D) patients we observed a dysregulation of the Treg cell population as well as a decrease in HPGD expression in these cells compared to healthy, age-matched controls. Taken together, these data indicate that both in humans and in the murine system, HPGD expression in Treg cells might be involved in metabolic regulation. Finally, we analyzed the role of the Treg cell specific transcription factor mesenchyme homeobox 1 (MEOX1) for HPGD expression. We found that MEOX1 is highly upregulated in human Treg cells, especially after stimulation with interleukin (IL) 2. Furthermore, we could show that while MEOX1 expression, like HPGD, is regulated by FOXP3, a loss of MEOX1 does not affect HPGD expression, thus disproving our hypothesis that HPGD may be regulated by the transcription factor MEOX1. Taken together, we could describe that HPGD is an important mediator of Treg cell suppression, independently of MEOX1. We found that a Treg cell specific deletion of Hpgd in the mouse leads to a dysregulation of the metabolism, and that HPGD levels are significantly decreased in Treg cells isolated from the peripheral blood of T2D patients compared to Treg cells isolated from healthy subjects

    Amtliche Bekanntmachungen 50. Jahrgang, Nr. 6

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    Beschluss des Fakultätsrats der Philosophischen Fakultät der Rheinischen Friedrich-Wilhelms-Universität Bonn vom 15. Januar 2020 zum Außerkraftsetzen der Prüfungsordnung für die weiterbildenden Masterstudiengänge „Rechtspsychologie“ und „Verkehrs-psychologie“ vom 28. August 201

    Impact of chronic liver inflammation on adaptive immune responses to viral infection

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    A common complication in patients suffering from chronic liver inflammation and fibrosis is the enhanced susceptibility to viral infections and weak responses to vaccination, which are associated with significant co-morbidities. To unravel the cellular and molecular mechanisms underlying the impaired adaptive immune response during liver fibrosis, we investigated the T cell-mediated immune responses to lymphocytic choriomenigitis virus (LCMV) infection, as well as in response to OVA/PolyI:C vaccination. Using the bile duct ligation (BDL) murine model of chronic liver inflammation and fibrosis, we found that chronic liver damage is associated with persistence of infection, recapitulating the clinical situation in humans. Hallmarks of the defective anti-viral immunity in these mice were reduced expansion of LCMV-specific CD4+ and CD8+ T cells, decreased expression of IFNγ and TNFα, as well as an elevated co-expression of the exhaustion marker PD1 together with LAG3 and TIM3 in virus-specific T cells from the spleen and liver. The reduced number of LCMV-specific CD4+ and CD8+ T cells are due to decreased proliferation as well as increased apoptosis among SMARTA T cells. Additionally, LCMV-specific CD4+ and CD8+ T cells display reduced mitochondrial fitness, characterized by a higher proportion of cells containing depolarized (i.e. dysfunctional) mitochondria, and producing high levels of superoxide among SMARTA and P14 T cells from mice with liver fibrosis. After OVA/PolyI:C vaccination antigen-specific CD4+ and CD8+ T cells were similarly reduced in numbers in mice with liver fibrosis and displayed reduced production of IFNγ, TNFα and IL-2. Interestingly, endogenous OVA-specific CD8+ T cells, as well as transferred OT-I T cells also show severe signs of exhaustion after vaccination, which manifested in elevated levels and co-expression of PD-1 and LAG3, as well as PD-1 and TIM3 in mice with liver fibrosis. The future goal of this project is to identify key molecular pathways induced by chronic liver damage that can be therapeutically modulated to promote anti-viral immunity and to improve vaccination responses in patients suffering from chronic liver inflammation and fibrosis


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