Environmental governance in a contested state:the influence of European Union and other external actors on energy sector regulation in Kosovo

This article examines environmental governance in Kosovo, with a particular focus on the energy sector. The article considers the degree to which the emerging model of environmental governance is characterised by hierarchical and non-hierarchical modes of coordination. We examine the roles of a number of domestic institutions and actors – ministries, agencies, and regulatory bodies– and the influence of external actors, including the EU, the US, and Serbia. The EU is building Kosovo’s own hierarchical governance capacity by strengthening domestic institutions, whilst the US focuses primarily on market liberalization, whilst simultaneously supporting EU efforts. Moreover, environmental policy change is not wholly or predominantly driven by domestic actors, which can partly be attributed to Kosovo’s limited domestic sovereignty. We conclude that the emerging model of environmental governance in Kosovo is characterized by a weak hierarchy, partly as a result of external actor involvement, which disincentivises the government from responding to domestic non-state actor pressure

Differential Impact of Tetratricopeptide Repeat Proteins on the Steroid Hormone Receptors

Tetratricopeptide repeat (TPR) motif containing co-chaperones of the chaperone Hsp90 are considered control modules that govern activity and specificity of this central folding platform. Steroid receptors are paradigm clients of Hsp90. The influence of some TPR proteins on selected receptors has been described, but a comprehensive analysis of the effects of TPR proteins on all steroid receptors has not been accomplished yet.We compared the influence of the TPR proteins FK506 binding proteins 51 and 52, protein phosphatase-5, C-terminus of Hsp70 interacting protein, cyclophillin 40, hepatitis-virus-B X-associated protein-2, and tetratricopeptide repeat protein-2 on all six steroid hormone receptors in a homogeneous mammalian cell system. To be able to assess each cofactor's effect on the transcriptional activity of on each steroid receptor we employed transient transfection in a reporter gene assay. In addition, we evaluated the interactions of the TPR proteins with the receptors and components of the Hsp90 chaperone heterocomplex by coimmunoprecipitation. In the functional assays, corticosteroid and progesterone receptors displayed the most sensitive and distinct reaction to the TPR proteins. Androgen receptor's activity was moderately impaired by most cofactors, whereas the Estrogen receptors' activity was impaired by most cofactors only to a minor degree. Second, interaction studies revealed that the strongly receptor-interacting co-chaperones were all among the inhibitory proteins. Intriguingly, the TPR-proteins also differentially co-precipitated the heterochaperone complex components Hsp90, Hsp70, and p23, pointing to differences in their modes of action.The results of this comprehensive study provide important insight into chaperoning of diverse client proteins via the combinatorial action of (co)-chaperones. The differential effects of the TPR proteins on steroid receptors bear on all physiological processes related to steroid hormone activity

Studies of a co-chaperone of the androgen receptor, FKBP52, as candidate for hypospadias

BACKGROUND: Hypospadias is a common inborn error of the male urethral development, for which the aetiology is still elusive. Polymorphic variants in genes involved in the masculinisation of male genitalia, such as the androgen receptor, have been associated with some cases of hypospadias. Co-regulators of the androgen receptor start being acknowledged as possible candidates for hormone-resistance instances, which could account for hypospadias. One such molecule, the protein FKBP52, coded by the FKBP4 gene, has an important physiological role in up-regulating androgen receptor activity, an essential step in the development of the male external genitalia. The presence of hypospadias in mice lacking fkbp52 encouraged us to study the sequence and the expression of FKBP4 in boys with isolated hypospadias. PATIENTS AND METHODS: The expression of FKBP52 in the genital skin of boys with hypospadias and in healthy controls was tested by immunohistochemistry. Mutation screening in the FKBF4 gene was performed in ninety-one boys with non syndromic hypospadias. Additionally, two polymorphisms were typed in a larger cohort. RESULTS: Immunohistochemistry shows epithelial expression of FKBP52 in the epidermis of the penile skin. No apparent difference in the FKBP52 expression was detected in healthy controls, mild or severe hypospadias patients. No sequence variants in the FKBP4 gene have implicated in hypospadias in our study. CONCLUSION: FKBP52 is likely to play a role in growth and development of the male genitalia, since it is expressed in the genital skin of prepubertal boys; however alterations in the sequence and in the expression of the FKBP4 gene are not a common cause of non-syndromic hypospadias

Re-visualising international relations:Audio-visual projects and direct encounters with the political in security studies tla

In this paper we discuss how an innovative audio-visual project was adopted to foster active, rather than declarative learning, in critical International Relations (IR). First, we explore the aesthetic turn in IR, to contrast this with forms of representation that have dominated IR scholarship. Second, we describe how students were asked to record short audio or video projects to explore their own insights through aesthetic and non-written formats. Third, we explain how these projects are understood to be deeply embedded in social science methodologies. We cite our inspiration from applying a personal sociological imagination, as a way to counterbalance a ‘marketised’ slant in higher education, in a global economy where students are often encouraged to consume, rather than produce knowledge. Finally, we draw conclusions in terms of deeper forms of student engagement leading to new ways of thinking and presenting new skills and new connections between theory and practice

Suppression of GATA-3 Nuclear Import and Phosphorylation: A Novel Mechanism of Corticosteroid Action in Allergic Disease

Peter Barnes and colleagues show that corticosteroids have a potent inhibitory effect on GATA-3 via two interacting mechanisms that suppress Th2 cytokine expression. This novel mechanism of corticosteroid action may help explain the efficacy of corticosteroids in allergic diseases

Expression and Regulation of the Fkbp5 Gene in the Adult Mouse Brain

BACKGROUND: Chronic stress has been found to be a major risk factor for various human pathologies. Stress activates the hypothalamic-pituitary-adrenal (HPA) axis, which is tightly regulated via, among others, the glucocorticoid receptor (GR). The activity of the GR is modulated by a variety of proteins, including the co-chaperone FK506 binding protein 51 (FKBP5). Although FKBP5 has been associated with risk for affective disorders and has been implicated in GR sensitivity, previous studies focused mainly on peripheral blood, while information about basal distribution and induction in the central nervous system are sparse. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, we describe the basal expression pattern of Fkbp5 mRNA in the brain of adult male mice and show the induction of Fkbp5 mRNA via dexamethasone treatment or different stress paradigms. We could show that Fkbp5 is often, but not exclusively, expressed in regions also known for GR expression, for example the hippocampus. Furthermore, we were able to induce Fkbp5 expression via dexamethasone in the CA1 and DG subregions of the hippocampus, the paraventricular nucleus (PVN) and the central amygdala (CeA). Increase of Fkbp5 mRNA was also found after restrained stress and 24 hours of food deprivation in the PVN and the CeA, while in the hippocampus only food deprivation caused an increase in Fkbp5 mRNA. CONCLUSIONS/SIGNIFICANCE: Interestingly, regions with a low basal expression showed higher increase in Fkbp5 mRNA following induction than regions with high basal expression, supporting the hypothesis that GR sensitivity is, at least partly, mediated via Fkbp5. In addition, this also supports the use of Fkbp5 gene expression as a marker for GR sensitivity. In summary, we were able to give an overview of the basal expression of fkbp5 mRNA as well as to extend the findings of induction of Fkbp5 and its regulatory influence on GR sensitivity from peripheral blood to the brain

Co-chaperones are limiting in a depleted chaperone network

To probe the limiting nodes in the chaperoning network which maintains cellular proteostasis, we expressed a dominant negative mutant of heat shock factor 1 (dnHSF1), the regulator of the cytoplasmic proteotoxic stress response. Microarray analysis of non-stressed dnHSF1 cells showed a two- or more fold decrease in the transcript level of 10 genes, amongst which are the (co-)chaperone genes HSP90AA1, HSPA6, DNAJB1 and HSPB1. Glucocorticoid signaling, which requires the Hsp70 and the Hsp90 folding machines, was severely impaired by dnHSF1, but fully rescued by expression of DNAJA1 or DNAJB1, and partially by ST13. Expression of DNAJB6, DNAJB8, HSPA1A, HSPB1, HSPB8, or STIP1 had no effect while HSP90AA1 even inhibited. PTGES3 (p23) inhibited only in control cells. Our results suggest that the DNAJ co-chaperones in particular become limiting in a depleted chaperoning network. Our results also suggest a difference between the transcriptomes of cells lacking HSF1 and cells expressing dnHSF1

Analysis of Chaperone mRNA Expression in the Adult Mouse Brain by Meta Analysis of the Allen Brain Atlas

The pathology of many neurodegenerative diseases is characterized by the accumulation of misfolded and aggregated proteins in various cell types and regional substructures throughout the central and peripheral nervous systems. The accumulation of these aggregated proteins signals dysfunction of cellular protein homeostatic mechanisms such as the ubiquitin/proteasome system, autophagy, and the chaperone network. Although there are several published studies in which transcriptional profiling has been used to examine gene expression in various tissues, including tissues of neurodegenerative disease models, there has not been a report that focuses exclusively on expression of the chaperone network. In the present study, we used the Allen Brain Atlas online database to analyze chaperone expression levels. This database utilizes a quantitative in situ hybridization approach and provides data on 270 chaperone genes within many substructures of the adult mouse brain. We determined that 256 of these chaperone genes are expressed at some level. Surprisingly, relatively few genes, only 30, showed significant variations in levels of mRNA across different substructures of the brain. The greatest degree of variability was exhibited by genes of the DnaJ co-chaperone, Tetratricopeptide repeat, and the HSPH families. Our analysis provides a valuable resource towards determining how variations in chaperone gene expression may modulate the vulnerability of specific neuronal populations of mammalian brain

Oznaczanie aldehydów w depozycji mokrej

The paper presents two sample preparation procedures for the determination of aldehydes in wet deposition. In both cases the 2,4-dinitrophenylhydrazine derivatization and solid phase extraction were applied. The derivatization in method A was applied before the extraction, the extraction in method B was carried out with simultaneous derivatisation. Accuracy of both methods was evaluated on the basis of the analysis of aqueous solutions of selected carbonyl compounds. Both methods were characterized by good recovery, however, due to the precision of the method expressed as RSD for testing of environmental samples the method B was used. The analysis of environmental samples showed significant differences in the concentrations of aldehydes in wet deposition, depending on the location of the sampling point. In the case of samples taken from agricultural areas the predominant aldehydes were formaldehyde and acetaldehyde. Formaldehyde was from 31% to 47% of the determined compounds. While in samples collected near a traffic source, in the deposition acrolein was determined at the levels from 62% to 64% of the identified compounds.W pracy przedstawiono dwie procedury przygotowania próbek mokrej depozycji do oznaczeń aldehydów. W obydwóch przypadkach zastosowano derywatyzację 2,4-dinitrofenylohydrazyną oraz ekstrakcję do fazy stałej. W metodzie A derywatyzacja poprzedzała ekstrakcję, w metodzie B ekstrakcję prowadzono z równoczesną derywatyzacją. Na podstawie analiz wodnych roztworów wybranych związków karbonylowych oceniono precyzję obydwóch metod. Ze względu na odzysk oraz wartość względnego odchylenia do analiz próbek środowiskowych pobranych z obszarów silnie uprzemysłowionych i rolniczych wybrano metodę B. Analiza próbek środowiskowych wykazała znaczne zróżnicowanie stężeń aldehydów w mokrej depozycji w zależności od lokalizacji punktu pobierania próbek. W przypadku próbek pobranych z obszarów rolniczych dominującymi aldehydami były formaldehyd i acetaldehyd. Formaldehyd stanowił od 31% do 47% oznaczonych związków. Podczas gdy w próbkach pobranych w pobliżu źródeł komunikacyjnych w depozycji stwierdzono udział akroleiny w oznaczonych aldehydach na poziomie od 62% do 64% oznaczonych związków