The Challenge of Governing Natural Resources : A Social Network Analysis of Actors’ Collaboration in Ghana’s Petroleum Sector

The PhD thesis investigates the extent of collaboration among actors in Ghana’s petroleum sector. Previous research has either focused on the socio-economic changes enforced upon local communities in close proximity to the offshore petroleum fields, or on the institutional framework that aims to govern the petroleum industry. While the first strand of literature criticizes the negative impacts on local communities, analyses of the second strand overwhelmingly praise Ghana as a role model for “good” petroleum governance as the government aims to include non-state actors as advisory and controlling bodies in resource governance. In development literature and international development collaboration, such multi-actor approaches are argued to increase the effectiveness in governing natural resources and to better address communities’ interests considering the role of non-state actors as citizens’ representatives beyond the state. Yet, so far, a conceptual argument why state and non-state actors should collaborate and an empirical investigation how they collaborate are outstanding. At the same time, it remains unclear which actors involved in petroleum governance are perceived as representatives by affected communities. My thesis is a first attempt to address these gaps. Based on exchange theory, the thesis scrutinizes which actors in Ghana’s petroleum sector (aim to) steer petroleum resources and deriving revenues, which of these actors affected communities perceive as representatives of their interests and to what extent these actors attain their proclaimed goal to collaboratively govern the petroleum sector. The analysis of two novel data sets tackle these questions. Primary survey data compiled with 333 expropriated land owners and farmers are used to investigate the abilities of petroleum actors to represent affected communities’ interests. The extent of collaboration among petroleum actors is methodically appropriated with Social Network Analysis (SNA). The necessary network data were generated by the means of a structured questionnaire testing six different means of collaboration among 29 actors from the public, private, donor, traditional, civil society and media sector. Based on the triangulation of qualitative and quantitative data analysis, I argue that effective representation and collaboration is constrained by an executive dominance, a deviation between communities’ interests and actors’ goals in petroleum governance, contestation rather than collaboration among non-state actors, and a lack of long-term, collaborative strategies among all actors. Hence, while Ghana is far from experiencing the devastating consequences of the so-called “resource curse”, actors so far fall short of their objective to jointly govern the petroleum sector

Engineering the enantioselective reduction of citral isomers in NCR ene reductase

Ene reductases are members of the Old Yellow Enzyme family catalyzing the asymmetric reduction of activated C=C double bonds with high stereoselectivities. The selective reduction of citral to (R)-citronellal is of special interest as it is a cheap precursor for the industrially relevant aroma chemical (-)-menthol. The unsaturated aldehyde citral consists of the two isomers neral (Z-isomer) and geranial (E-isomer). Enantioconvergent reduction of both substrates to (R)-citronellal, the precursor for (-) menthol, is so far unachieved in catalysis. However, the Zymomonas mobilis ene reductase NCR exclusively reduces both citral isomers to (S)-citronellal with good activity. Recently, we observed a good mutability in NCR ene reductase. The principal possibility of an enzymatic enantioconvergent citral reduction in NCR inspired us to invert the selectivity by a semi-rational enzyme engineering approach. Please click Additional Files below to see the full abstract

Social Innovations in the extended Lake Constance area – an overview of the current activities

In recent years the importance of social innovation for societies is rising. Therefore, the European Union realized, that political goals can be successfully achieved through social innovations.1 The concept is offering solutions for social challenges broadly based and in a variety of different fields Thus, the focus of this paper will be to identify social innovation activities in the Lake Constance area and the problems which are being solved through those activities. It will therefore provide a quantitative analysis of the identified projects including the main idea of the activity as well as information about the innovators. The key outcomes of this paper are, that social innovators are mainly focusing on current political challenges such as the refugee crisis. Problems which the society is already facing for a longer period of time, are less focused. It could further be identified, that the majority of social innovators are students or graduates. Also, most of the activities have their origin in bigger cities such as Stuttgart, Karlsruhe or Heidelberg

Biosynthesis of the allelopathic inhibitor 7-deoxysedoheptulose in Synechococcus elongatus PCC 7942 and its mode of inhibition in the shikimate pathway

Cyanobakterien sind Produzenten einer Vielzahl von Sekundärmetaboliten mit verschiedenen Funktionen. Dazu zählt beispielsweise auch die Synthese allelopathischer Inhibitoren, die in der gleichen ökologischen Nische lebende Organismen hemmen. Üblicherweise werden solche Metaboliten von filamentösen Cyanobakterien mittels großer Gencluster hergestellt. Überraschenderweise wurde kürzlich ein bioaktiver Desoxy-Zucker, genauer 7-Desoxysedoheptulose (7dSh), aus dem Kulturüberstand des einzelligen Cyanobakteriums Synechococcus elongatus PCC 7942 (S. elongatus) isoliert. In der vorliegenden Arbeit wurde durch die Analyse des Kulturüberstandes mittels Gaschromatographie-gekoppelter Massenspektrometrie, Fütterungsexperimenten, sowie Knockout Mutanten der Biosyntheseweg von 7dSh aufgeklärt. Dieses leitet sich von 5-Desoxyadenosin (5dAdo) ab, einem inhibitorischen Nebenprodukt radikalischer SAM Enzyme, die in allen drei Domänen des Lebens vorkommen. 5dAdo wird dabei lediglich durch promiskuitive Aktivität von Enzymen des Primärstoffwechsels metabolisiert. Dies führt zunächst zu einer Ausscheidung und Akkumulation von 5-Desoxyribose, gefolgt von einer Anreicherung von 7dSh. Da S. elongatus ein kleines Genom ohne kanonische Gencluster für die Sekundärmetabolitsynthese besitzt, erlaubt diese Strategie die Synthese eines bioaktiven Moleküls direkt aus einem „Abfall“-Produkt des Primärstoffwechsels. Dies findet vollständig durch promiskuitive Enzymaktivitäten statt, ohne dass daran ein spezifisches Gencluster involviert wäre. Diese Entdeckung stellt die klassische Sicht auf die Synthese von Sekundärmetaboliten als Produkte spezifischer Gencluster in Frage und erweitert damit die Bandbreite an bioaktiven Molekülen. Neben der Aufklärung des Biosyntheseweges von 7dSh wurde hiermit auch ein alternativer Recyclingweg für 5dAdo, der bisher noch nicht bekannt war, beschrieben. Im zweiten Teil dieser Arbeit wurde außerdem das Zielenzym von 7dSh in der Zelle, die Dehydrochinat-Synthase, das zweite Enzym des Shikimatwegs, bestätigt. Durch die Entwicklung eines in vitro Inhibitionsassays mit aufgereinigtem Enzym konnte gezeigt werden, dass dieses Molekül die DHQS kompetitiv hemmt. Dabei liegen die Inhibitionskonstante wie auch der IC50-Wert im niedrigeren µM Bereich. 7dSh inhibiert das Wachstum verschiedener Cyanobakterien. Es kann aber auch das Wachstum auskeimender Pflanzen auf Erde hemmen, was für eine potenzielle Verwendung als Herbizid sprechen könnte. Außerdem konnte gezeigt werden, dass die hemmende Wirkung von 7dSh auf Anabaena variabilis ATCC 29413 und Synechocystis sp. PCC 6803 über eine effektive und rasche Aufnahme mittels strukturell verschiedener, promiskuitiver Zuckertransporter zustande kommt. Beteiligt daran sind ein Fructose ABC-Transporter bzw. eine Glucose-Permease. Spontane Mutationen im jeweiligen Kohlenhydrattransporter führen zu einem Verlust der 7dSh-Sensitivität, gehen aber auch mit einem Verlust der Fähigkeit des heterotrophen Wachstums einher. Aufgrund dieser Ergebnisse wird angenommen, dass 7dSh der erste allelopathische Inhibitor des Shikimatwegs ist, welcher S. elongatus in der Verteidigung seiner ökologischen Nische unterstützt.Cyanobacteria are known as producers of a wide range of secondary metabolites with various functions. This includes the synthesis of allelopathic inhibitors, which suppress the growth of other organisms within the same ecological niche. These compounds are usually produced by filamentous cyanobacteria via huge gene clusters. Nevertheless, a bioactive deoxy-sugar, namely 7-deoxysedoheptulose (7dSh), was recently isolated from the culture supernatant of the unicellular cyanobacterium Synechococcus elongatus PCC 7942 (S. elongatus). In this work the biosynthetic pathway of 7dSh formation was elucidated by means of supernatant analysis via gas chromatography-mass spectrometry, feeding experiments and knockout mutants. 7dSh derives from 5-deoxyadenosine (5dAdo), an inhibitory by-product of radical SAM enzymes, which are present in all domains of life. 5dAdo is metabolized by solely promiscuous activity of enzymes of the primary metabolism, resulting in the excretion first of 5-deoxyribose and subsequently of 7dSh into the culture supernatant. This strategy enables S. elongatus, which has a small, stream-lined genome lacking canonical gene clusters for the synthesis of secondary metabolites, to produce an allelopathic inhibitor from a “waste” product of primary metabolism by enzymatic promiscuity, without involving a specific gene cluster. This discovery challenges the view on the biosynthesis of bioactive molecules as sole products of biosynthetic gene clusters and expands the range of bioactive compounds which can be synthesized. Additionally, with the elucidation of the biosynthesis of 7dSh, an alternative pathway for 5dAdo salvage was discovered, which had previously not been described. In the second part of this work, the intracellular target of 7dSh, the dehydroquinate synthase, which is the second enzyme of the shikimate pathway, was confirmed. By the development of an in vitro inhibition assay using purified enzyme, it was shown that 7dSh inhibits the enzyme in a competitive manner, with an inhibition constant as well as an IC50-value in the lower µM range. Besides the inhibition of other cyanobacteria, 7dSh also inhibits the growth of germinating plant seedlings on soil, indicating that it might be used as an herbicide. Furthermore, it was shown that in Anabaena variabilis ATCC 29413 and Synechocystis sp. PCC 6803, the inhibitory effect of this molecule is correlated with an effective uptake via structurally different, promiscuous sugar transporters – a fructose ABC-transporter or a glucose permease. Spontaneous mutations in these transport proteins can result in the loss of 7dSh sensitivity, however the capability of heterotrophic growth is disabled at the same time. 7dSh can therefore be assumed to represent the first allelopathic inhibitor targeting the shikimate pathway, supporting S. elongatus in its niche competition

Säkerhetisering av migration i EU - En studie om hur migranternas mänskliga säkerhet påverkas av européernas samhälleliga osäkerhet

Det blir svårare och svårare för migranter att på laglig väg ta sig till Europa och människor dör varje dag vid Europas gränser. Detta beror, som vi ser det, bland annat på att migrationsfrågan har säkerhetiserats och åtgärder som i normala fall inte accepteras, rättfärdigas för att skydda säkerheten inom Europa. Vi utgår i denna uppsats från de två säkerhetsbegreppen samhällelig säkerhet och mänsklig säkerhet och vårt syfte är att se inom vilka aspekter som säkerhetisering av migration har skett och se vad detta får för påverkan på immigranternas mänskliga säkerhet. De områden vi identifierat där migrationsfrågan har säkerhetiserats är kriminell, ekonomisk, välfärd och kulturell. Denna säkerhetisering påverkar migranterna både på vägen mot Europa och när de väl är där och påverkar såväl illegala som legala migranter. Det vi kan se är att immigranternas mänskliga säkerhet påverkas negativt av säkerhetiseringen av migration då européernas samhälleliga säkerhet prioriteras migranternas mänskliga säkerhet

Catechol-O-methyltransferase (COMT) Genotype Affects Age-Related Changes in Plasticity in Working Memory: A Pilot Study

Objectives. Recent work suggests that a genetic variation associated with increased dopamine metabolism in the prefrontal cortex (catechol-O-methyltransferase Val158Met; COMT) amplifies age-related changes in working memory performance. Research on younger adults indicates that the influence of dopamine-related genetic polymorphisms on working memory performance increases when testing the cognitive limits through training. To date, this has not been studied in older adults.Method. Here we investigate the effect of COMT genotype on plasticity in working memory in a sample of 14 younger (aged 24-30 years) and 25 older (aged 60-75 years) healthy adults. Participants underwent adaptive training in the -back working memory task over 12 sessions under increasing difficulty conditions. Results. Both younger and older adults exhibited sizeable behavioral plasticity through training ( < .001), which was larger in younger as compared to older adults ( < .001). Age-related differences were qualified by an interaction with COMT genotype ( < .001), and this interaction was due to decreased behavioral plasticity in older adults carrying the Val/Val genotype, while there was no effect of genotype in younger adults.Discussion. Our findings indicate that age-related changes in plasticity in working memory are critically affected by genetic variation in prefrontal dopamine metabolism

Thoughts on opportunities in high-energy nuclear collisions

This document reflects thoughts on opportunities from high-energy nuclear collisions in the 2020s.Comment: 10 pages, pd

Properties of hot and dense matter from relativistic heavy ion collisions

We review the progress achieved in extracting the properties of hot and dense matter from relativistic heavy ion collisions at the relativistic heavy ion collider (RHIC) at Brookhaven National Laboratory and the large hadron collider (LHC) at CERN. We focus on bulk properties of the medium, in particular the evidence for thermalization, aspects of the equation of state, transport properties, as well as fluctuations and correlations. We also discuss the in-medium properties of hadrons with light and heavy quarks, and measurements of dileptons and quarkonia. This review is dedicated to the memory of Gerald E. Brown

Inhibition of lysyl oxidases synergizes with 5-azacytidine to restore erythropoiesis in myelodysplastic and myeloid malignancies

Limited response rates and frequent relapses during standard of care with hypomethylating agents in myelodysplastic neoplasms (MN) require urgent improvement of this treatment indication. Here, by combining 5-azacytidine (5-AZA) with the pan-lysyl oxidase inhibitor PXS-5505, we demonstrate superior restoration of erythroid differentiation in hematopoietic stem and progenitor cells (HSPCs) of MN patients in 20/31 cases (65%) versus 9/31 cases (29%) treated with 5-AZA alone. This effect requires direct contact of HSPCs with bone marrow stroma components and is dependent on integrin signaling. We further confirm these results in vivo using a bone marrow niche-dependent MN xenograft model in female NSG mice, in which we additionally demonstrate an enforced reduction of dominant clones as well as significant attenuation of disease expansion and normalization of spleen sizes. Overall, these results lay out a strong pre-clinical rationale for efficacy of combination treatment of 5-AZA with PXS-5505 especially for anemic MN

Loss-of-function variants in CUL3 cause a syndromic neurodevelopmental disorder

Purpose De novovariants inCUL3(Cullin-3 ubiquitin ligase) have been strongly associated with neurodevelopmental disorders (NDDs), but no large case series have been reported so far. Here we aimed to collect sporadic cases carrying rare variants inCUL3,describe the genotype-phenotype correlation, and investigate the underlying pathogenic mechanism.MethodsGenetic data and detailed clinical records were collected via multi-center collaboration. Dysmorphic facial features were analyzed using GestaltMatcher. Variant effects on CUL3 protein stability were assessed using patient-derived T-cells.ResultsWe assembled a cohort of 35 individuals with heterozygousCUL3variants presenting a syndromic NDD characterized by intellectual disability with or without autistic features. Of these, 33 have loss-of-function (LoF) and two have missense variants.CUL3LoF variants in patients may affect protein stability leading to perturbations in protein homeostasis, as evidenced by decreased ubiquitin-protein conjugatesin vitro. Specifically, we show that cyclin E1 (CCNE1) and 4E-BP1 (EIF4EBP1), two prominent substrates of CUL3, fail to be targeted for proteasomal degradation in patient-derived cells.ConclusionOur study further refines the clinical and mutational spectrum ofCUL3-associated NDDs, expands the spectrum of cullin RING E3 ligase-associated neuropsychiatric disorders, and suggests haploinsufficiency via LoF variants is the predominant pathogenic mechanism