Weber in the Balkans: contested party–state relations in reforming the civil service in Albania and FYR Macedonia, 2000–13

Defence date: 17 May 2018Examining Board: Professor László Bruszt, formerly EUI/ Scuola Normale Superiore ; Professor Hanspeter Kriesi, European University Institute ; Professor Isabela Mares, Columbia University ; Professor Jan-Meyer Sahling, Nottingham UniversityWhat drives politicians to adopt and implement civil service reforms differently? What explains the variation in politicization and professionalization in the state bureaucracy across countries and across governments? Why do certain incumbents politicize less the state administration and others professionalize more? This thesis answers these questions by contributing to the literature of postcommunist studies, comparative politics and political economy in two ways. The thesis first unpacks outcomes that stand between the patrimonial and Weberian bureaucracy along a two-dimensional framework on levels of politicization and professionalization, in order to explain the political incentives and circumstances that explain this variation. Challenging current explanations on state reform as a by-product of political competition or historical legacies the thesis argues that political parties’ incentives play a central role in reforming bureaucracies. More precisely, I argue that while, politicization, in terms of political hiring and firing, is a function of resources’ needs of parties to strengthen their own organizational survival, professionalization is a function of the electoral pressure on parties to deliver public good. The incentives political parties face to provide more effectively public goods and the incentives to use state resources for organizational needs might combine in various ways, yielding different combinations of professionalization and politicization in bureaucratic design. To explore this argument, the dissertation examines levels of politicization and professionalization in Albania and Macedonia1 over time in the period between 2000-2013. The dissertation finds that Macedonia in contrast to Albania ended up in a highly incompetent administration because of parties’ usage of ethnic salience in order to electorally win, without the need to deliver on public good. Conversely, Albania developed a comparatively more competent administration, as incumbents had to deliver some public good in order to maintain power in comparison to competitors. Interestingly, in both countries, levels of politicization varied across time and across sectors based on party organization age, showing that older parties have lower need to use state patronage for organizational survival and hence were more capable of improving the state bureaucracy

Monitoring local well-being in environmental interventions: a consideration of practical trade-offs

Within the field of environmental management and conservation, the concept of well-being is starting to gain traction in monitoring the socio-economic and cultural impact of interventions on local people. Here we consider the practical trade-offs policy makers and practitioners must navigate when utilizing the concept of well-being in environmental interventions. We first review current concepts of well-being before considering the need to balance the complexity and practical applicability of the definition used and to consider both positive and negative components of well-being. A key determinant of how well-being is operationalized is the identity of the organization wishing to monitor it. We describe the trade-offs around the external and internal validity of different approaches to measuring well-being and the relative contributions of qualitative and quantitative information to understanding well-being. We explore how these trade-offs may be decided as a result of a power struggle between stakeholders. Well-being is a complex, multi-dimensional, dynamic concept that cannot be easily defined and measured. Local perspectives are often missed during the project design process as a result of the more powerful voices of national governments and international NGOs, so for equity and local relevance it is important to ensure these perspectives are represented at a high level in project design and implementation

Inhibition of BET proteins and epigenetic signaling as a potential treatment for osteoporosis

International audienceHistone modifications are important for maintaining the transcription program. BET proteins, an important class of " histone reading proteins " , have recently been described as essential in bone biology. This study presents the therapeutic opportunity of BET protein inhibition in osteoporosis. We find that the pharmacological BET protein inhibitor JQ1 rescues pathologic bone loss in a post-ovariectomy osteoporosis model by increasing the trabecular bone volume and restoring mechanical properties. The BET protein inhibition suppresses osteoclast differentiation and activity as well as the osteoblastogenesis in vitro. Moreover, we show that treated non-resorbing osteoclasts could still activate osteoblast differentiation. In addition, specific inhibition of BRD4 using RNA interference inhibits osteoclast differentiation but strongly activates osteoblast mineralization activity. Mechanistically, JQ1 inhibits expression of the master osteoclast transcription factor NFATc1 and the transcription factor of osteoblast Runx2. These findings strongly support that targeting epigenetic chromatin regulators such as BET proteins may offer a promising alternative for the treatment of bone-related disorders such as osteoporosis

Influence of N-methyl pyrrolidone on the activity of the pulp-dentine complex and bone integrity during osteoporosis

AIM To analyze the effect of systemic application of N-methyl pyrrolidone (NMP) on the pulp-dentine complex and on the jawbone of ovariectomized rats. METHOD Female Sprague-Dawley rats were randomly divided into a sham-operated group (Sham n=6) and an estrogen depletion by ovariectomy (OVX n=12) group. In 6 of the ovariectomized animals N-methyl pyrrolidone (NMP) in phosphate-buffered saline (PBS) was administered systemically weekly by intraperitoneal injection (i.p.); the other 6 were injected with PBS (Veh). After 15 weeks of injections the jaw bones were collected and pulps extracted from the incisors teeth. Histology was used to determine pre-dentine thickness in teeth and radiography to determine alveolar bone mass. Immunohistological staining and RT-PCR were performed to verify the presence and localization of the odontoblast specific dentine sialoprotein and to quantify its expression in the dentine pulp complex. Mandibular cortical width and mandibular height was evaluated by means of X-ray analysis. Statistical analysis was performed with analysis of variance (ANOVA). RESULTS Both pre-dentine (P=0.029) and alveolar bone structures (P=0.049) were significantly reduced due to estrogen deficiency in OVX Veh and OVX NMP treatment normalized these parameters to the Sham level. DSPP expression in OVX NMP animals was significantly higher (P=0.046) than in OVX Veh. X-ray analysis confirmed that ovariectomy significantly reduced the mandibular cortical width in the OVX Veh group compared to the Sham Veh and OVX NMP (P=0.020). CONCLUSION N-methyl pyrrolidone (NMP) had a remarkable anti-osteoporotic ability preserving the activity in the pulp-dentine complex and preventing jawbone loss. These effects make NMP a promising candidate for the preservation of the activity of the pulp-dentine complex and the jawbone thickness in postmenopausal females. This article is protected by copyright. All rights reserved

N,N Dimethylacetamide a drug excipient that acts as bromodomain ligand for osteoporosis treatment

N,N-Dimethylacetamide (DMA) is a water-miscible solvent, FDA approved as excipient and therefore widely used as drug-delivery vehicle. As such, DMA should be devoid of any bioactivity. Here we report that DMA is epigenetically active since it binds bromodomains and inhibits osteoclastogenesis and inflammation. Moreover, DMA enhances bone regeneration in vivo. Therefore, our in vivo and in vitro data reveal DMA’s potential as an anti-osteoporotic agent via the inhibition of osteoclast mediated bone resorption and enhanced bone regeneration. Our results highlight the potential therapeutic benefits of DMA and the need for reconsideration of previous reports where DMA was used as an ‘inactive’ drug-delivery vehicle

N -methyl pyrrolidone (NMP) inhibits lipopolysaccharide-induced inflammation by suppressing NF-κB signaling

Objective: N-methyl pyrrolidone (NMP), a small bioactive molecule, stimulates bone formation and inhibits osteoclast differentiation and bone resorption. The present study was aimed to evaluate the anti-inflammatory potentials of NMP on the inflammatory process and the underlying molecular mechanisms in RAW264.7 macrophages. Materials and methods: RAW264.7 macrophages and mouse primary bone marrow macrophages (mBMMs) were used as an in vitro model to investigate inflammatory processes. Cells were pre-treated with or without NMP and then stimulated with lipopolysaccharides (LPS). The productions of cytokines and NO were determined by proteome profiler method and nitrite analysis, respectively. The expressions of nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were measured by Western blotting and/or qPCR. Western blot, ELISA-base reporter assay, and immunofluorescence were used to evaluate the activation of MAP kinases and NF-κB. Results: LPS-induced mRNA expressions of TNF-α, IL-1β, IL-6, iNOS, and COX-2 were inhibited by NMP in a dose-dependent manner. NMP also suppressed the LPS-increased productions of iNOS and NO. The proteome profiler array showed that several cytokines and chemokines involved in inflammation and up-regulated by LPS stimulation were significantly down-regulated by NMP. Additionally, this study shows that the effect of NMP is mediated through down-regulation of NFκB pathway. Conclusions: Our results show that NMP inhibits the inflammatory mediators in macrophages by an NFκB-dependent mechanism, based on the epigenetical activity of NMP as bromodomain inhibitor. In the light of its action on osteoblast and osteoclast differentiation process and its anti-inflammatory potential, NMP might be used in inflammation-related bone loss

Effects of stem cell factor on cell homing during functional pulp regeneration in human immature teeth

Conventional root canal treatment in immature permanent teeth can lead to early tooth loss in children because root formation is discontinued. We investigated whether the stem cell factor (SCF) could facilitate cell homing in the pulpless immature root canal and promote regeneration of a functional pulp. In vitro, human mesenchymal stem cells (hMSCs) were exposed to SCF at various concentrations for assessing cell migration, proliferation, and differentiation toward odonto/osteoblasts by 3D-chemotaxis slides, WST-1 assay, and alkaline phosphatase activity, respectively. Fibrin gels were used to deliver 15 μg/mL SCF for in vivo experiments. The release kinetic of SCF was assessed in vitro. Two corresponding human immature premolars, with or without SCF, were placed at rat calvariae for 6 and 12 weeks. All tooth specimens were either analyzed histologically and the percentage of tissue ingrowth determined or the cells were extracted from the pulp space, and the mRNA level of DMP1, DSPP, Col1, NGF, and VEGF were assessed by quantitative polymerase chain reaction. In the presence of SCF, we saw an increase in hMSCs directional migration, proliferation, and odonto/osteogenic differentiation. SCF also increased the extent of tissue ingrowth at 6 weeks but not at 12 weeks. However, at this time point, the formed tissue appeared more mature in samples with SCF. In terms of gene transcription, DMP1, Col1, and VEGF were the significantly upregulated genes, while DSPP and NGF were not affected. Our results suggest that SCF can accelerate cell homing and the maturation of the pulp-dentin complex in human immature teeth