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Political science has not remained on the side of the internationalisation road. While continental European political science was criticised for not being internationalised enough in the beginning of this century, much progress has been done since then. This symposium discusses the state of play of the internationalisation trend(s) in European political science. Building on the data collected within the COST programme PROSEPS, the contributions show that we have made progress toward building a scholarly community across Europe. European political research has, on a number aspects, become a more collective endeavour deployed across Europe. Opportunities for cumulative knowledge-building and intellectual exchange are, partially at least, supported by internationalisation. These opportunities have significantly increased over the last two decades. We are, nevertheless, not there yet. The articles shed light on a number of challenges and pitfalls on the path towards a truly Europe-wide political science. [ABSTRACT FROM AUTHOR]

The concept of internationalisation, when referring to the work of social scientists within academic institutions, takes on different meanings and involves different activities. This contribution aims to shed light on the international activities of political scientists across Europe and to investigate the various meanings and practices of internationalisation. The analysis relies on the PROSEPS survey, involving some 1,800 political scientists across 37 European countries. We identify three distinct profiles of international scholars: the networked researcher, the editorial manager, and the traveller. These profiles differ according to 1) the building of international research networks, 2) the involvement in the activities of the international publishing industry, 3) the research and teaching exchanges with foreign academic institutions. Determinants, such as gender, family status, career stage, availability of institutional and financial support, and geographical location, are considered as potential drivers or inhibitors of internationalisation. Our analysis shows that the internationalisation of academic practices follows contrasting paths according to the type of international profile. [ABSTRACT FROM AUTHOR]

It is well known that the solar gravitational field can be considered as a telescope with a prime focus at locations beyond 550 au. In this work, we present a new derivation of the wave-optical properties of the system by adapting the arrival-time formalism from gravitational lensing. At the diffraction limit, the angular resolution is similar to that of a notional telescope with the diameter of the Sun, and the maximum light amplification is 8π4 GM ⊙/(c 2λ), enough to detect a |$1\,$| W laser on Proxima Centauri b pointed in the general direction of the Sun. Extended sources, however, would be blurred by the wings of the point spread function into the geometrical-optics regime of gravitational lensing. Broad-band sources would have to further contend with the solar corona. Imaging an exoplanet surface as advocated in the literature, without attempting to reach the diffraction limit, appears achievable. For diffraction-limited imaging (sub-km scales from 100 pc), nearby neutron stars appear to be most plausible targets. [ABSTRACT FROM AUTHOR]

The lack of cumulative knowledge challenges scientific relevance and the capacity for problem solving. Despite the multiplication of instrument typologies, a shared comparative understanding of what instruments are, how they function and what effect they produce is still lacking. This article assesses the extent to which major policy instrument theories are fit for comparative analysis. It identifies five main methodological and theoretical trade-offs that should be considered when elaborating on the research design of comparative policy research: parsimony, reliability, analytical purpose, comparative perspective and performance assessment. [ABSTRACT FROM AUTHOR]

European institutionalisation of public health policy has never been more topical than in the COVID-19 era. One European agency has come to the fore: the European Centre for Disease Prevention and Control (ECDC). Historically, the ECDC's mandate has expanded only gradually and the management of transboundary health crises has remained ultimately in the hands of Member States. The unprecedented severity of COVID-19 has led the European Commission to propose an extension of the ECDC's mandate. This study assesses the expansion of the formal and informal mandates of the ECDC over 15 years to contextualise the catalytic impact of COVID-19. It is found that while institutional change occurs in the aftermath of a transboundary health crisis, it builds on a long-term process of gradual institutionalisation that is accelerated by the crisis acting as a catalyst but not fully determined by it. [ABSTRACT FROM AUTHOR]

Gender and politics research faces a crossroad in the age of populism. On the one hand, gender and sexuality research is on the way to institutionalisation across a growing number of academic systems in Europe. On the other, gender and sexuality research has become increasingly contested and attacked, and has become the bête noire of the populist and radical right. This contribution contends that gender research is under threat not only because of the gender component, but also because of the scholarly research. There are thus lessons to be drawn for the wider discipline of political science. This article first sketches out the dualization in the institutionalization of gender-related research. It then situates the hostility towards gender and sexuality research in the broader (and growing) opposition to gender + and sexual + equality. It concludes with some preliminary observations about the how this hostility may be part of a wider contestation of academic expertise and scholarly knowledge that is being led, at least in part, by populist forces of all stripes. [ABSTRACT FROM AUTHOR]

• TBT and TPT induce the transcription of 11β-HSD2 in JEG-3 cells. • Upregulation of 11β-HSD2 results in reduced cortisol-dependent activation of the GR. • RXRα is involved in the TBT and TPT induced effect on 11β-HSD2. • Fludioxonil and chlorotriphenylsilane activate RXRα and induce 11β-HSD2 expression. Exposure to the environmental pollutants organotins is of toxicological concern for the marine ecosystem and sensitive human populations, including pregnant women and their unborn children. Using a placenta cell model, we investigated whether organotins at nanomolar concentrations affect the expression and activity of 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2). 11β-HSD2 represents a placental barrier controlling access of maternal glucocorticoids to the fetus. The organotins tributyltin (TBT) and triphenyltin (TPT) induced 11β-HSD2 expression and activity in JEG-3 placenta cells, an effect confirmed at the mRNA level in primary human trophoblast cells. Inhibition/knock-down of retinoid X receptor alpha (RXRα) in JEG-3 cells reduced the effect of organotins on 11β-HSD2 activity, mRNA and protein levels, revealing involvement of RXRα. Experiments using RNA and protein synthesis inhibitors indicated that the effect of organotins on 11β-HSD2 expression was direct and caused by increased transcription. Induction of placental 11β-HSD2 activity by TBT, TPT and other endocrine disrupting chemicals acting as RXRα agonists may affect placental barrier function by altering the expression of glucocorticoid-dependent genes and resulting in decreased availability of active glucocorticoids for the fetus, disturbing development and increasing the risk for metabolic and cardiovascular complications in later life. [ABSTRACT FROM AUTHOR]

The principal paradox of comparative public policy has remained over the years: there is no clear and broadly shared definition of the field. This article engages with the debate about what comparative public policy is from a distinctive perspective. Drawing from a systematic analysis of published research articles that maps out the usual comparative suspects, it reflects on what comparative public policy does and does not do in terms of comparative scope and country range, and the extent to which the limitations in the comparative scope matter for cumulative knowledge, theory building and the consolidation of the field. The article discusses different strategies to address the challenge of extending the range of comparative analysis. [ABSTRACT FROM AUTHOR]

Background Mutations in the HSD17B3 gene are associated with a 46,XY disorder of sexual development (46,XY DSD) as a result of low testosterone production during embryogenesis. Aim To elucidate the molecular basis of the disorder by chemically analyzing four missense mutations in HSD17B3 (T54A, M164T, L194P, G289S) from Egyptian patients with 46,XY DSD. Methods Expression plasmids for wild-type 17β-hydroxysteroid hydrogenase type 3 (17β-HSD3) and mutant enzymes generated by site-directed mutagenesis were transiently transfected into human HEK-293 cells. Protein expression was verified by western blotting and activity was determined by measuring the conversion of radiolabeled Δ 4 -androstene-3,17-dione to testosterone. Application of a homology model provided an explanation for the observed effects of the mutations. Outcomes Testosterone formation by wild-type and mutant 17β-HSD3 enzymes was compared. Results Mutations T54A and L194P, despite normal protein expression, completely abolished 17β-HSD3 activity, explaining their severe 46,XY DSD phenotype. Mutant M164T could still produce testosterone, albeit with significantly lower activity compared with wild-type 17β-HSD3, resulting in ambiguous genitalia or a microphallus at birth. The substitution G289S represented a polymorphism exhibiting comparable activity to wild-type 17β-HSD3. Sequencing of the SRD5A2 gene in three siblings bearing the HSD17B3 G289S polymorphism disclosed the homozygous Y91H mutation in the former gene, thus explaining the 46,XY DSD presentations. Molecular modeling analyses supported the biochemical observations and predicted a disruption of cofactor binding by mutations T54A and M164T and of substrate binding by L196P, resulting in the loss of enzyme activity. In contrast, the G289S substitution was predicted to disturb neither the three-dimensional structure nor enzyme activity. Clinical Translation Biochemical analysis of mutant 17β-HSD3 enzymes is necessary to understand genotype-phenotype relationships. Strengths and Limitations Biochemical analysis combined with molecular modeling provides insight into disease mechanism. However, the stability of mutant proteins in vivo cannot be predicted by this approach. Conclusion The 17β-HSD3 G289S substitution, previously reported in other patients with 46,XY DSD, is a polymorphism that does not cause the disorder; thus, further sequence analysis was required and disclosed a mutation in SRD5A2, explaining the cause of 46,XY DSD in these patients. Engeli RT, Tsachaki M, Hassan HA, et al. Biochemical Analysis of Four Missense Mutations in the HSD17B3 Gene Associated With 46,XY Disorders of Sex Development in Egyptian Patients. J Sex Med 2017;14:1165–1174. [ABSTRACT FROM AUTHOR]

Parabens are effective preservatives widely used in cosmetic products and processed food, with high human exposure. Recent evidence suggests that parabens exert estrogenic effects. This work investigated the potential interference of parabens with the estrogen-activating enzyme 17β-hydroxysteroid dehydrogenase (17β-HSD) 1 and the estrogen-inactivating 17β-HSD2. A ligand-based 17β-HSD2 pharmacophore model was applied to screen a cosmetic chemicals database, followed by in vitro testing of selected paraben compounds for inhibition of 17β-HSD1 and 17β-HSD2 activities. All tested parabens and paraben-like compounds, except their common metabolite p-hydroxybenzoic acid, inhibited 17β-HSD2. Ethylparaben and ethyl vanillate inhibited 17β-HSD2 with IC50 values of 4.6 ± 0.8 and 1.3 ± 0.3 μM, respectively. Additionally, parabens size-dependently inhibited 17β-HSD1, whereby hexyl- and heptylparaben were most active with IC50 values of 2.6 ± 0.6 and 1.8 ± 0.3 μM. Low micromolar concentrations of hexyl- and heptylparaben decreased 17β-HSD1 activity, and ethylparaben and ethyl vanillate decreased 17β-HSD2 activity. However, regarding the very rapid metabolism of these compounds to the inactive p-hydroxybenzoic acid by esterases, it needs to be determined under which conditions low micromolar concentrations of these parabens or their mixtures can occur in target cells to effectively disturb estrogen effects in vivo. [ABSTRACT FROM AUTHOR]

17β-Hydroxysteroid dehydrogenase type 2 (17β-HSD2) converts the potent estrogen estradiol into the weakly active keto form estrone. Because of its expression in bone, inhibition of 17β-HSD2 provides an attractive strategy for the treatment of osteoporosis, a condition that is often caused by a decrease of the active sex steroids. Currently, there are no drugs on the market targeting 17β-HSD2, but in multiple studies, synthesis and biological evaluation of promising 17β-HSD2 inhibitors have been reported. Our previous work led to the identification of phenylbenzenesulfonamides and -sulfonates as new 17β-HSD2 inhibitors by ligand-based pharmacophore modeling and virtual screening. In this study, new molecules representing this scaffold were synthesized and tested in vitro for their 17β-HSD2 activity to derive more profound structure-activity relationship rules. [ABSTRACT FROM AUTHOR]

Objectives: In addition to its use as a volume filler, fat grafting may have a potential role in wound healing based on the concentration of growth factors in the lipoaspirate. In this study, we compare the quantitative and qualitative concentration of the various growth factors and adipokines using the Shippert or the Coleman techniques to prepare the lipoaspirate. Methods: We measured leptin, adiponectin and the growth factors, i.e., acidic fibroblast growth factor (aFGF), basic FGF (bFGF), keratinocyte growth factor (KGF), bone morphogenetic protein-2 (BMP-2) and vascular endothelial growth factor (VEGF) by ELISA in solid and liquid fractions obtained with both techniques in human fat obtained with Coleman technique and Shippert technique. Results: All of these peptides, except BMP-2, were detected in relevant quantities in the solid fraction. The Coleman but not the Shippert technique resulted in statistically higher adiponectin concentrations in the solid tissue fraction. The other four growth factors occurred in significantly higher concentrations in the solid fractions compared to the liquid fractions, independent of the processing technique. Conclusion: In summary, we demonstrated that KGF, aFGF, bFGF and VEGF, as well as leptin and adiponectin, are contained in fat suspensions obtained by liposuction and in the supernatant. Only the concentration of adiponectin was in the range reported to contribute to wound healing. [ABSTRACT FROM AUTHOR]

Objective: Low cardiorespiratory fitness (CRF) predisposes one to cardiovascular disease and type 2 diabetes in part independently of body weight. Given the close relationship between intrahepatic lipid content (IHL) and insulin sensitivity, we hypothesized that the direct relationship between fitness and insulin sensitivity may be explained by IHL.Research Design and Methods: We included 138 overweight to obese, otherwise healthy subjects (aged 43.6 +/- 8.9 years, BMI 33.8 +/- 4 kg/m(2)). Body composition was estimated by bioimpedance analyses. Abdominal fat distribution, intramyocellular, and IHL were assessed by magnetic resonance spectroscopy and tomography. Incremental exercise testing was performed to estimate an individual's CRF. Insulin sensitivity was determined during an oral glucose tolerance test.Results: For all subjects, CRF was related to insulin sensitivity (r = 0.32, P < 0.05), IHL (r = -0.27, P < 0.05), and visceral (r = -0.25, P < 0.05) and total fat mass (r = -0.32, P < 0.05), but not to intramyocellular lipids (r = -0.08, NS). Insulin sensitivity correlated significantly with all fat depots. In multivariate regression analyses, independent predictors of insulin sensitivity were IHL, visceral fat, and fitness (r(2) = -0.43, P < 0.01, r(2) = -0.34, and r(2) = 0.29, P < 0.05, respectively). However, the positive correlation between fitness and insulin sensitivity was abolished after adjustment for IHL (r = 0.16, NS), whereas it remained significant when adjusted for visceral or total body fat. Further, when subjects were grouped into high versus low IHL, insulin sensitivity was higher in those subjects with low IHL, irrespective of fitness levels.Conclusions: Our study suggests that the positive effect of increased CRF on insulin sensitivity in overweight to obese subjects may be mediated indirectly through IHL reduction. [ABSTRACT FROM AUTHOR]

Selective laser melting of high γ′ strengthened superalloys such as IN738LC is of huge interest for stationary gas turbine applications. In order to identify the influence of the powder characteristics on SLM processing, several batches of commercially available IN738LC powder made by gas and water atomization were characterized with respect to particle size distribution, morphology and chemical composition. The different powders were processed under equal conditions by selective laser melting (SLM) and the build quality was assessed by quantitative image analysis. Samples made out of the water atomized (WA) powder showed a higher porosity after SLM compared to the spherical gas atomized (GA) powders due to the greater irregular morphology of the powder. The porosity of the gas atomized powder batches was found to be influenced by the flow behavior of the powder. Large differences were observed for the hot cracking susceptibility of the different powder batches during SLM processing. The cracking density was correlated to the chemical composition and it was found that the minor element Si has a large influence on the SLM processability of the IN738LC powder. A strict control of this element is important to decrease the hot cracking tendency and extends the SLM processing window of this alloy. [ABSTRACT FROM AUTHOR]

Life-threatening diseases like malignant tumours are associated with considerable existential distress. Little is known about the factors that promote resilience within these individuals. This longitudinal qualitative partner study aimed to analyse resilience as per Antonovsky's sense of coherence. Eight patients with malignant melanoma and their partners were interviewed. They were asked about their coping strategies, attitudes towards the meaning of life and their cancer, and comprehension of what is happening to them. The questions were asked shortly after their diagnosis was made and 6 months later. All interviews were audio-taped and later transcribed and analysed according to the method of qualitative content analysis described by P. Mayring. At baseline, the majority of statements made (261; patients = 141/spouses = 120) related to coping/manageability of disease, with only 26 statements (patients = 15/spouses = 11) related to meaning and 127 (patients = 64/spouses = 63) to comprehension. There were no significant differences between the responses of patients and their partners and no significant changes in the number of statements during the 6-month interview. The most significant theme that emerged was manageability of disease, with distraction the most commonly utilised coping skill. The comprehension and meaning themes were far less prevalent. Hence, support should focus on disease and situational manageability. [ABSTRACT FROM AUTHOR]

Mutations in the HSD17B3 gene resulting in 17β-hydroxysteroid dehydrogenase type 3 (17β-HSD3) deficiency cause 46, XY Disorders of Sex Development (46, XY DSD). Approximately 40 different mutations in HSD17B3 have been reported; only few mutant enzymes have been mechanistically investigated. Here, we report novel compound heterozygous mutations in HSD17B3 , composed of the nonsense mutation C206X and the missense mutation G133R, in three Tunisian patients from two non-consanguineous families. Mutants C206X and G133R were constructed by site-directed mutagenesis and expressed in HEK-293 cells. The truncated C206X enzyme, lacking part of the substrate binding pocket, was moderately expressed and completely lost its enzymatic activity. Wild-type 17β-HSD3 and mutant G133R showed comparable expression levels and intracellular localization. The conversion of Δ4-androstene-3,17-dione (androstenedione) to testosterone was almost completely abolished for mutant G133R compared with wild-type 17β-HSD3. To obtain further mechanistic insight, G133 was mutated to alanine, phenylalanine and glutamine. G133Q and G133F were almost completely inactive, whereas G133A displayed about 70% of wild-type activity. Sequence analysis revealed that G133 on 17β-HSD3 is located in a motif highly conserved in 17β-HSDs and other short-chain dehydrogenase/reductase (SDR) enzymes. A homology model of 17β-HSD3 predicted that arginine or any other bulky residue at position 133 causes steric hindrance of cofactor NADPH binding, whereas substrate binding seems to be unaffected. The results indicate an essential role of G133 in the arrangement of the cofactor binding pocket, thus explaining the loss-of-function of 17β-HSD3 mutant G133R in the patients investigated. [ABSTRACT FROM AUTHOR]

This article investigates the factors that drive governments to pay attention to gender equality issues and place them upon executive agendas. In line with studies of the dynamics of issue attention, which demonstrate the importance of investigating variability in the attention policy makers give to issue demands across policy domains, this article argues that policy issues related to gender equality are multidimensional and patterns in executive attention vary across the different types of gender issues. Multidimensionality of gender equality issues reflects different dynamics in agenda-setting as different issues invoke contrasting constellations of political representation, institutional friction and veto points. To investigate this variation, this article proposes a twofold distinction between class-based and status-based gender equality issues and assesses the validity of three sets of explanations for when gender issues succeed in reaching executive agendas: women in politics, party ideology and economic performance. Drawing on governmental attention datasets from the Comparative Agendas Project, a systematic comparative quantitative analysis of the determinants of gender equality issue attention in five Western European countries is conducted. The main findings confirm that the mechanisms through which different types of gender equality issues gain executive attention differ according to the kind of the gender equality demand. Costly class-based gender equality issues are more likely to receive executive attention when the economy is performing well, when there is a strong presence of Social Democrats and when there is a high proportion of female MPs. In contrast, economic performance, party politics and women's parliamentary presence do not seem to exert any impact on status-based issues. Instead, critical actors in the government seem to be the strongest driver for attention over this second type of gender equality issue. This study contributes a gendered dimension to the policy agendas scholarship, adding theoretical and empirical depth to the understanding of how non-core issues secure their place on full governmental agendas. By focusing on how to secure governmental attention for gender equality issues, the article makes a major contribution to understanding the initial genesis of gender equality policies. [ABSTRACT FROM AUTHOR]

Objective: Weight cycling is a prevalent phenomenon in obese individuals. There is evidence that temperamental factors are associated with obesity and subgroups among the obese have been identified based on reactive and regulative aspects of temperament. Methods: We aimed at investigating the association between reactive and regulative aspects of temperament and severe weight cycling in overweight and obese individuals of a representative German population sample (n = 923). Participants completed questionnaires assessing weight parameters including BMI and weight cycling, sensitivity to punishment and to reward (BIS/BAS scales), self-regulatory abilities (effortful control scale), depressive symptoms, and binge eating. Results: Severe weight cycling was more common in women, and was associated with higher reward sensitivity, higher current and maximum-ever BMI, higher weight suppression, more depressive symptoms, and a higher prevalence of binge eating. In contrast, sensitivity to punishment and effortful control were not associated with severe weight cycling. Also, the interaction between sensitivity to reward and effortful control did not predict weight cycling. Discussion: Higher reward sensitivity might not only render individuals vulnerable for weight regain but might also be associated with a higher frequency of weight loss attempts due to the putative rewarding properties of the initial success in weight loss at the early stages of a diet. Temperamental factors should be considered in the treatment of obesity. [ABSTRACT FROM AUTHOR]

Many research studies analysing the effects of multi-graded classes have stated the need for a description of mixed-age teaching for pedagogical reasons. We tried to fill this gap by presenting a theoretical concept transferred onto a measurement model with seven typical elements of mixed-age teaching practices as a basis for future research. Within this structural-equation model, we were also able to trace the relationships between these practices. The empirical data derives from a teacher survey ( N = 280) conducted as part of the Swiss-Austrian project, “Schools in Alpine Regions 2”. [ABSTRACT FROM AUTHOR]

We developed a simple tool for ranking chemical hazard-food pairs to assist policy makers and risk managers selecting the hazard-food pairs that deserve more attention and need to be monitored during food safety inspections. The tool is based on the derivation of a “Priority Index” (PI) that results from the ratio of the potency of the hazard and the consumer exposure. The potency corresponds to a toxicity reference value of the hazard, whereas the exposure results from the combination of the concentration of the hazard in the food, and the food consumption. Tool’s assumptions and limitations are demonstrated and discussed by ranking a dataset of 13 mycotoxins in 26 food items routinely analyzed in Switzerland. The presented ranking of mycotoxin-food pairs has to be considered as relative due to scarce exposure data availability, and uncertainties in toxicity reference values. However, this representative example allows demonstrating the simplicity and the ability of the PI tool to prioritize chemical hazard-food pairs. [ABSTRACT FROM AUTHOR]

Securing executive attention for new policy demands is notoriously difficult as governmental agendas are crowded by established or ‘core’ policy issues. This article investigates whether it is harder for new and costly policy issues to reach the government agenda when the economy is performing badly. It examines whether, and the extent to which, costly gender equality issues regarding women’s access to the labour market, equal treatment at work and care activities, are more likely to achieve executive attention when the economy is performing well. Using the Comparative Policy Agendas database, a systematic, quantitative analysis is conducted of when and why policies promoting sex equality in the division of labour reach executive agendas. The findings confirm that advocacy for costly gender equality measures is easier to make in times of economic growth. It is also found that female representation in parliament strengthens advocacy for executive attention and reduces friction on policy agenda change. [ABSTRACT FROM PUBLISHER]

17β-Hydroxysteroiddehydrogenase 2 (17β-HSD2) catalyzesthe inactivation of estradiol into estrone. This enzyme is expressedonly in a few tissues, and therefore its inhibition is consideredas a treatment option for osteoporosis to ameliorate estrogen deficiency.In this study, ligand-based pharmacophore models for 17β-HSD2inhibitors were constructed and employed for virtual screening. Fromthe virtual screening hits, 29 substances were evaluated in vitrofor 17β-HSD2 inhibition. Seven compounds inhibited 17β-HSD2with low micromolar IC50values. To investigate structure–activityrelationships (SAR), 30 more derivatives of the original hits weretested. The three most potent hits, 12, 22, and 15, had IC50values of 240 nM, 1 μM,and 1.5 μM, respectively. All but 1 of the 13 identified inhibitorswere selective over 17β-HSD1, the enzyme catalyzing conversionof estrone into estradiol. Three of the new, small, synthetic 17β-HSD2inhibitors showed acceptable selectivity over other related HSDs,and six of them did not affect other HSDs. [ABSTRACT FROM AUTHOR]

Highlights: [•] Dose development in feeding studies with constant compound concentrations was analyzed for rat strains. [•] Feed intake per animal is constant lifelong, hence feed intake per bodyweight decreases as rats grow. [•] Growing rats therefore experience a steep dose decrement. [•] Toxicity/exposure duration relationships should be interpreted in view of this dose decrement. [ABSTRACT FROM AUTHOR]

Background: Obesity is a risk factor for various types of infectious diseases and cancer. The increase in adipose tissue causes alterations in both adipogenesis and the production of adipocyte-secreted proteins (adipokines). Since natural killer (NK) cells are the host’s primary defense against virus-infected and tumor cells, we investigated how adipocyte-conditioned medium (ACM) affects functions of two distinct human NK cell subsets. Methods: Isolated human peripheral blood mononuclear cells (PBMCs) were cultured with various concentrations of human and murine ACM harvested on two different days during adipogenesis and analyzed by fluorescent-activated cell sorting (FACS). Results: FACS analyses showed that the expression of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), granzyme A (GzmA) and interferon (IFN)-γ in NK cells was regulated in a subset-specific manner. ACM treatment altered IFN-γ expression in CD56dim NK cells. The production of GzmA in CD56bright NK cells was differentially affected by the distinct adipokine compositions harvested at different states of adipogenesis. Comparison of the treatment with either human or murine ACM revealed that adipokine-induced effects on NK cell expression of the leptin receptor (Ob-R), TRAIL and IFN-γ were species-specific. Conclusion: Considering the growing prevalence of obesity and the various disorders related to it, the present study provides further insights into the roles human NK cell subsets play in the obesity-associated state of chronic low-grade inflammation. [ABSTRACT FROM AUTHOR]

Abstract: Here we present a processing route to produce multi-structured ceramic foams based on the combination of particle-stabilized foams with polymeric sponges to produce positive and negative templating structures. Polyester sponges are infiltrated with freshly produced calcium aluminate–alumina foams and upon sintering either positive templating structures are produced when wetting the sponges, or negative templating foams with a percolating pore network are obtained when completely filling the sponges. Additionally, by combining different layers of these particle-stabilized foam infiltrated sponges, various different structures can be produced, including sandwich structures, pore size gradients, and ceramic bone-like structures applying to different types of bone. The particle-stabilized foams used were in situ self-hardening calcium aluminate cement enriched alumina foams to obtain crack-free samples with pore interconnections and tailorable pore sizes. [Copyright &y& Elsevier]

Background: Excessive myocardial triglyceride (MTG) content in obesity and type 2 diabetes is associated with impaired cardiac function. Previous studies suggest that MTG could be mobilized through lifestyle interventions. We assessed influences of moderate dietary weight loss in non diabetic obese and overweight women on MTG content and cardiac function. Methods: We selected a subgroup of 38 women from the B-SMART study population. The B-SMART study compared weight loss and associated metabolic and cardiovascular markers with reduced-carbohydrate and reduced-fat hypocaloric diets. Selected subjects had completed a cardiac magnetic resonance (MR) scan including imaging and proton spectroscopy to assess cardiac structure and function as well as MTG content. Results: An average weight reduction of 5.4±4.3kg at six months was associated with a relative decrease of MTG of 25% (from 0.72±0.29% at baseline to 0.54±0.23% at follow-up, p<0.001). The response was similar with carbohydrate and fat restriction. Diastolic function expressed as ratio of peak filling rate in E- and A-Phase (PFRE/PFRA) was unchanged. Reductions of left atrial size (from 21.9±4.0cm2 to 20.0±3.7cm2, p=0.002), the normalized ratio of PFRE and early diastolic lengthening velocity PLV (from 8.2±2.6 to 7.5±2.5, p<0.001) and fat free mass (from 55.1±6.9kg to 52.7±6.5kg, p=0.007) reflected altered cardiac volume loading after diet, but did not correlate to MTG content. Conclusions: Moderate dietary weight loss significantly reduced MTG content in women with uncomplicated overweight or obesity. Macronutrient composition of the diet did not significantly affect the extent of MTG reduction. [ABSTRACT FROM AUTHOR]

Objective To explore whether increased adipocytederived serum fatty acid binding protein 4 (FABP4) predisposes to cardiac remodelling and left ventricular dysfunction in human obesity. Design Cross-sectional investigation. Setting Academic clinical research centre. Patients 108 overweight and obese non-diabetic women (body-mass index 33±5 kg/m2). Main outcome measures Relationship between serum FABP4 and abdominal adipose tissue quantified by MRI. Relationship between serum FABP4 and left ventricular morphology and function assessed by cardiac MRI. Results FABP4 was independently associated with visceral abdominal adipose tissue (ß=0.34, p<0.01) and subcutaneous abdominal adipose tissue (ß=0.22, p<0.05). After stratification into serum FABP4 tertiles, left ventricular masses were 92±16 g, 86±13 g and 81 ±12 g in women with high, intermediate and low FABP4 concentrations ( p<0.01), respectively. Longitudinal systolic function was reduced by 8% in women with intermediate and high versus low FABP4 concentrations ( p<0.01), whereas ejection fraction did not differ among tertiles (p=0.5). In multivariate linear analysis FABP4 remained an independent predictor of left ventricular mass (ß=0.17, p<0.05) and reduced longitudinal fractional shortening (ß=0.21, p<0.05). Conclusions In overweight and obese women, FABP4 showed an independent association with parameters of left ventricular remodelling. [ABSTRACT FROM AUTHOR]

An interest-driven account of embryonic stem cell research would, given the considerable financial and scientific concerns, likely predict regulations to converge towards permissive policies. However, across Western Europe, national regulations of embryonic stem cell research vary considerably, from general bans to permissive policies. There is a lack of systematic accounting for the non-convergence, and the sparse attempts at explanation are contradictory. Drawing on qualitative comparative analysis and configurational causality, we assess the interaction of a number of explanatory factors. Our empirical analysis reveals the importance of one factor in particular, path-dependence, insofar as prior policies on assisted reproduction exert a strong and systematic effect on the subsequent regulation of embryonic stem cell research. [ABSTRACT FROM PUBLISHER]

The growing interest in morality politics has spurred a large number of studies on individual morality issues and the gradual shift from restrictive to permissive regulation across Western Europe. Several studies have further pointed to the changing role of religion as the main cause of permissive policy shifts. However, seen in a comparative perspective across four countries and five morality issues, the move towards permissiveness poses more of a puzzle than a simple shift. Religion and secularization do not impact on regulation directly, but are filtered through a policy dynamic in which the essential factor is whether or not the party system contains a conflict line between secular and confessional parties. Countries without confessional parties, here the United Kingdom and Denmark, surprisingly end up less permissive than countries with strong confessional parties, here the Netherlands and Spain, because the former group lacks the conflict line necessary to politicize morality issues [ABSTRACT FROM PUBLISHER]

Cardiac natriuretic peptides (NP) are major activators of human fat cell lipolysis and have recently been shown to control brown fat thermogenesis. Here, we investigated the physiological role of NP on the oxidative metabolism of human skeletal muscle. NP receptor type A (NPRA) gene expression was positively correlated to mRNA levels of PPAR? coactivator-1a (PGC1A) and several oxidative phosphorylation (OXPHOS) genes in human skeletal muscle. Further, the expression of NPRA, PGC1A, and OXPHOS genes was coordinately upregulated in response to aerobic exercise training in human skeletal muscle. In human myotubes, NP induced PGC-1a and mitochondrial OXPHOS gene expression in a cyclic GMP-dependent manner. NP treatment increased OXPHOS protein expression, fat oxidation, and maximal respiration independent of substantial changes in mitochondrial proliferation and mass. Treatment of myotubes with NP recapitulated the effect of exercise training on muscle fat oxidative capacity in vivo. Collectively, these data show that activation of NP signaling in human skeletal muscle enhances mitochondrial oxidative metabolism and fat oxidation. We propose that NP could contribute to exercise training-induced improvement in skeletal muscle fat oxidative capacity in humans. [ABSTRACT FROM AUTHOR]

Local anaesthetic techniques and diagnostic imaging tools are currently used in conjunction with thorough physical and lameness examinations to diagnose sacroiliac disease (SID) in the horse. The deep and inaccessible location of the sacroiliac joint (SIJ), however, often renders diagnostic imaging modalities, such as radiography, nuclear scintigraphy and ultrasonography, unreliable in identifying sacroiliac problems. The equine clinician therefore often has to rely on positive results of local anaesthetic techniques to confirm a diagnosis of SID. Regional infiltration techniques have been described but result in a diffuse distribution of large volumes of local anaesthetic solution throughout the entire lumbosacroiliac region, which is nonspecific to the SIJ and has the potential to produce false positive results. Several periarticular injection approaches to the SIJ have recently been described. A combination of periarticular SIJ injections with the use of modest amounts of local anaesthetic solution provides increased SIJ specificity, but may lead to false negative results in cases where the pain originates from surrounding soft tissues. This article clarifies terminology related to sacroiliac injections, reviews current injection techniques, highlights the advantages and disadvantages of each approach, and investigates injectate volume considerations. [ABSTRACT FROM AUTHOR]

How best to govern reproduction is the subject of heated controversies and policies on abortion and reproductive technologies present strong variations. Through fuzzy-set qualitative comparative analysis, the article explores the interplay of institutional settings, Christian Democratic politics, women’s movement, and Christian opposition in France and Switzerland since the 1970s. If little evidence is found for any institutional impact on policies regarding abortion and reproductive technologies, the analysis confirms the growing influence of the medical profession over reproductive issues and shows that the success of the women’s movement has been fluctuating while prolife opposition seems to have gradually lost influence. [ABSTRACT FROM PUBLISHER]

Objective:To test the hypothesis that variations in trunk circumferences influence the accuracy of bioimpedance analysis (BIA) for assessment of percent fat mass (%FM).Subjects and Methods:%FM was predicted with BIA, and compared with air-displacement plethysmography (ADP) in a small sample of 35 overweight (OW), 21 normal weight and 8 underweight volunteers. Waist and hip circumferences were assessed, and 15 of the OW subjects were measured before and after weight reduction.Results:BIA and ADP provided similar cross-sectional estimates of group mean %FM (28.9±10.0 and 31.3±13.0%, respectively). However, within individuals, there were large between-method differences (DiffBIA−ADP) ranging from −13 to +13 %FM. Furthermore, we found a systematic bias of BIA related to the degree of adiposity. Consequently, %FM and fat mass loss during weight reduction in OW were underestimated with BIA when compared with ADP. Waist and hip circumferences were inversely associated with resistance (R) and reactance (P<0.01), and with DiffBIA−ADP (P<0.001). In women, the variability in hip circumference explained 76%, and in men, the variability in waist circumference explained 59% of DiffBIA−ADP.Conclusion:Resistance changes associated with variations in trunk circumferences decrease resistance, and therefore impair the accuracy of BIA to assess %FM. [ABSTRACT FROM AUTHOR]

The article presents a report on the first roach recovered from the Kota Formation assigned to a genus of Mesoblattinidae, a family well known from the Middle Jurassic through the Late Cretaceous including amber inclusions. The Archimesoblatta Vrsansky is an elongated mesoblattinid roaches with subparallel forewing margins, veins strongly curved proximally and with secondary branches present apically. The new species Archimesoblatta has relatively more simplified venation with only 15 branches to R and relative small size reaching only 9.5mm when complete. It expects richer abundance of material and more thorough characterization of the roach Archimesoblatta with further exploration in India.

Abstract: The effect of exposure duration on no observed adverse effect levels (NOAEL) and lowest observed adverse effect levels (LOAEL) in rodent pesticide feeding studies was evaluated. Ratios of NOAEL (and LOAEL), expressed as pesticide concentrations in feed, were calculated from subacute to subchronic, subchronic to chronic and subacute to chronic studies. There was no statistical significant effect of exposure duration on ratio distributions. Whereas geometric means of ratios were in a narrow range of 1.1–2.5, the geometric standard deviations and 95th percentiles increased with dose spacing of the involved studies. With the exception of carbamates, the chemical class of pesticides had no influence on the ratio distributions. However, the number of animals in the shorter-term study of ratio couples being ⩽1 was statistically significantly higher than in ratio couples being >1. Ratios ⩽1 may be partly explained by the dose decrement over time observed in feeding studies applying the test substances in constant concentrations. The dose decrement possibly converts initially toxic doses to less toxic doses beyond the subacute phase. Ratios >1 seem to be caused predominantly by differences in study design parameters. In dietary risk assessment, the acceptable daily intake (ADI) is compared to pesticide intake estimates based on mean food consumption (i.e. the so called theoretical maximum daily intake, TMDI) being orders of magnitude lower than actual food consumption on eating occasions for certain food commodities. As subacute, subchronic and chronic NOAEL (and LOAEL), expressed as pesticide concentration in feed did not differ statistically significantly, the TMDI as benchmark for the ADI may underestimate the significance of the toxicity of subacute exposure. [Copyright &y& Elsevier]

Background Obesity predisposes to heart failure and premature cardiovascular death, particularly in sedentary women. In animal models and in men with type 2 diabetes mellitus, impaired cardiac function is associated with myocardial triglyceride (MTG) accumulation. Lipotoxic injury from altered myocardial metabolism may be causative. Whether such association also exists in obese, non-diabetic women is unknown. Objective To explore the relation between MTG content, cardiac remodelling and cardiorespiratory fitness in obese, insulin-sensitive and insulin-resistant non-diabetic women. Design Cross-sectional investigation. Setting Academic clinical research centre. Patients 65 Overweight/obese and sedentary, but otherwise healthy women (body mass index 33±4 kg/m2; age 45±10 years). Interventions None. Main outcome measures Cardiac structure and function measured by cardiovascular magnetic resonance imaging and MTG content of the interventricular septum by 1H MR spectroscopy. Additional outcomes were cardiopulmonary fitness and insulin sensitivity during oral glucose tolerance testing. Results Insulin resistance (composite insulin sensitivity index (C-ISI) <4.6) was present in 29 women. MTG content was higher (0.83±0.30 vs 0.61±0.23, p=0.002) and left ventricular diastolic (p<0.01), but not systolic function was reduced in women with insulin resistance compared with insulin-sensitive women. The remodelling index defined as left ventricular mass divided by end-diastolic volume was increased in women with impaired glucose tolerance (p=0.006). Furthermore, cardiopulmonary fitness was equal in both groups, but was inversely correlated with MTG (r=-0.28, p=0.02). Conclusions In overweight and obese women, insulin resistance is associated with increased MTG content, cardiac remodelling and reduced diastolic function. [ABSTRACT FROM AUTHOR]

OBJECTIVE--Low cardiorespiratory fitness (CRF) predisposes one to cardiovascular disease and type 2 diabetes in part independently of body weight. Given the close relationship between intrahepatic lipid content (IHL) and insulin sensitivity, we hypothesized that the direct relationship between fitness and insulin sensitivity may be explained by IHL. RESEARCH DESIGN AND METHODS--We included 138 overweight to obese, otherwise healthy subjects (aged 43.6 ± 8.9 years, BMI 33.8 ± 4 kg/m2). Body composition was estimated by bioimpedance analyses. Abdominal fat distribution, intramyocellular, and IHL were assessed by magnetic resonance spectroscopy and tomography. Incremental exercise testing was performed to estimate an individual's CRF. Insulin sensitivity was determined during an oral glucose tolerance test. RESULTS--For all subjects, CRF was related to insulin sensitivity (r = 0.32, P < 0.05), IHL (r = -0.27, P < 0.05), and visceral (r = -0.25, P < 0.05) and total fat mass (r = -0.32, P < 0.05), but not to intramyocellular lipids (r = -0.08, NS). Insulin sensitivity correlated significantly with all fat depots. In multivariate regression analyses, independent predictors of insulin sensitivity were IHL, visceral fat, and fitness (r2 = -0.43, P < 0.01, 2 = -0.34, and 2 = 0.29, P < 0.05, respectively). However, the positive correlation between fitness and insulin sensitivity was abolished after adjustment for IHL (r = 0.16, NS), whereas it remained significant when adjusted for visceral or total body fat. Further, when subjects were grouped into high versus low IHL, insulin sensitivity was higher in those subjects with low IHL, irrespective of fitness levels. CONCLUSIONS--Our study suggests that the positive effect of increased CRF on insulin sensitivity in overweight to obese subjects may be mediated indirectly through IHL reduction. Diabetes 59:1640-1647, 2010 [ABSTRACT FROM AUTHOR]

An activation of the endocannabinoid system (ECS) in obesity with increased concentrations of endocannabinoids in several tissues and in the circulation is described in this review. This increased availability of endocannabinoids might stimulate cannabinoid receptors in a pathophysiological manner. The successful use of the cannabinoid receptor CB1 inverse agonists rimonabant and taranabant for weight loss and the treatment of obesity-associated metabolic disorders might well be through blocking this overstimulation of cannabinoid receptors. At present, no single mechanism has been identified that explains the increased bioavailability of endocannabinoids in obesity. Both increased synthesis and decreased degradation appear to operate in a species- and tissue-dependent manner, but many pieces of the puzzle still need to be collected. For example, most data show decreased fatty acid amide hydrolase (FAAH) expression and/or activity as a result of obesity or high-fat intake, but the endocannabinoid predominantly increased in tissues is 2-arachidonoylglycerol (2-AG), which is not degraded by FAAH in vivo. Furthermore, the influence of dietary fatty acids on the synthesis of endocannabinoids needs to be studied in much more detail. Although weight loss does not seem to influence activation of the endocannabinoid system (ECS) in human obesity, suggesting an underlying mechanisms independent of body weight, no such mechanism at the genetic level has yet been identified either. Thus, activation of the ECS is a hallmark of abdominal obesity, and explains the success of pharmacological CB1 blockade, but serious attempts have to be made to clarify the underlying mechanisms of this activation. [ABSTRACT FROM AUTHOR]

The endocannabinoid system has been suspected to contribute to the association of visceral fat accumulation with metabolic diseases. We determined whether circulating endocannabinoids are related to visceral adipose tissue mass in lean, subcutaneous obese, and visceral obese subjects (10 men and 10 women in each group). We further measured expression of the cannabinoid type 1 (CB1) receptor and fatty acid amide hydrolase (FAAH) genes in paired samples of subcutaneous and visceral adipose tissue in all 60 subjects. Circulating 2-arachidonoyl glycerol (2-AG) was significantly correlated with body fat (r = 0.45, P = 0.03), visceral fat mass (r = 0.44, P = 0.003), and fasting plasma insulin concentrations (r = 0.41, P = 0.001) but negatively correlated to glucose infusion rate during clamp (r = 0.39, P = 0.009). In visceral adipose tissue, CB1 mRNA expression was negatively correlated with visceral fat mass (r = 0.32, P = 0.01), fasting insulin (r = 0.48, P < 0.001), and circulating 2-AG (r = 0.5, P < 0.001), whereas FAAH gene expression was negatively correlated with visceral fat mass (r = 0.39, P = 0.01) and circulating 2-AG (r = 0.77, P < 0.001). Our findings suggest that abdominal fat accumulation is a critical correlate of the dysregulation of the peripheral endocannabinoid system in human obesity. Thus, the endocannabinoid system may represent a primary target for the treatment of abdominal obesity and associated metabolic changes. Diabetes 55:3053-3060, 2006 [ABSTRACT FROM AUTHOR]

Studies in mice suggest that adipocytes serve as glucose sensors and regulate systemic glucose metabolism through release of serum retinol-binding protein 4 (RBP4). This model has not been validated in humans. RBP4 was highly expressed in isolated mature human adipocytes and secreted by differentiating human adipocytes. In contrast to the animal data, RBP4 mRNA was downregulated in subcutaneous adipose tissue of obese women, and circulating RBP4 concentrations were similar in normal weight, overweight, and obese women (n = 74). RBP4 was positively correlated with GLUT4 expression in adipose tissue, independent of any obesity-associated variable. Five percent weight loss slightly decreased adipose RBP4 expression but did not influence circulating RBP4. In another set of experiments, we stratified patients (n = 14) by low or high basal fasting interstitial glucose concentrations, as determined by the microdialysis technique. Venous glucose concentrations were similar throughout oral glucose tolerance testing, and basal RBP4 expression in adipose tissue and serum RBP4 concentrations were similar in the groups with higher and lower interstitial glucose levels. Our findings point to profound differences between rodents and humans in the regulation of adipose or circulating RBP4 and challenge the notion that glucose uptake by adipocytes has a dominant role in the regulation of RBP4. Diabetes 55: 2805-2810, 2006 [ABSTRACT FROM AUTHOR]

ANG II applied to the interstitial space influences carbohydrate and lipid metabolism in a tissue-specific fashion. Thus endogenous ANG II may have a tonic effect on tissue metabolism that could be reversed with ANG II type 1 (AT1) receptor blockade, particularly during adrenergic stimulation. We studied 14 obese men. They were treated for 10 days with the AT1 receptor blocker irbesartan or with placebo in a double-blind and crossover fashion. At the end of each treatment period, we assessed skeletal muscle and adipose tissue metabolism using the microdialysis technique. The ethanol dilution technique was applied to follow changes in tissue blood flow. Measurements were obtained at baseline and during application of incremental isoproterenol concentrations through the microdialysis catheter. Blood pressure decreased from 133 ± 3/84 ± 3 to 128 ± 3/79 ± 2 mmHg for systolic and diastolic blood, respectively (P = 0.02 and 0.006, respectively) with AT1 receptor blockade. Isoproterenol perfusion caused a dose-dependent increase in dialysate glycerol in adipose tissue and in skeletal muscle. Irbesartan slightly reduced the isoproterenol-induced glycerol response in adipose tissue (P < 0.05 by ANOVA). Ethanol ratio, interstitial glucose supply, and lactate production in adipose tissue and skeletal muscle were similar with placebo and irbesartan. We conclude that AT1 receptor blockade in obese men does not reveal a major tonic ANG II effect on interstitial glucose supply, lipolysis, or glycolysis in skeletal muscle, either at rest or during β-adrenergic stimulation. Endogeneous ANG II may slightly increase adipose tissue lipolysis. The mechanism may promote the redistribution of triglycerides from adipose tissue toward other organs. [ABSTRACT FROM AUTHOR]

Obesity is the main risk factor for the development of type 2 diabetes. Activation of the central endocannabinoid system increases food intake and promotes weight gain. Blockade of the cannabinoid type 1 (CB-1) receptor reduces body weight in animals by central and peripheral actions; the role of the peripheral endocannabinoid system in human obesity is now being extensively investigated. We measured circulating endocannabinoid concentrations and studied the expression of CB-1 and the main degrading enzyme, fatty acid amide hydrolase (FAAH), in adipose tissue of lean (n = 20) and obese (n = 20) women and after a 5% weight loss in a second group of women (n = 17). Circulating levels of anandamide and 1/2-arachidonoylglycerol were increased by 35 and 52% in obese compared with lean women (P < 0.05). Adipose tissue mRNA levels were reduced by -34% for CB-1 and -59% for FAAH in obese subjects (P < 0.05). A strong negative correlation was found between FAAH expression in adipose tissue and circulating endocannabinoids. Circulating endocannabinoids and CB-1 or FAAH expression were not affected by 5% weight loss. The expression of CB-1 and FAAH was increased in mature human adipocytes compared with in preadipocytes and was found in several human tissues. Our findings support the presence of a peripheral endocannabinoid system that is upregulated in human obesity. [ABSTRACT FROM AUTHOR]

The Third International Symposium on Obesity and Hypertension (ISOH'03) was held on 23–25, October 2003 at the Max Delbruck Center for Molecular Medicine in Berlin-Buch, Germany. The meeting, which consisted largely of invited lectures, presented a state-of-the-art overview of the genetic and molecular mechanisms that link obesity and hypertension. The over 40 oral presentations were supplemented by around 90 poster presentations from 34 countries. The meeting was attended by around 250 participants from 54 countries. This paper briefly reviews the contents of the invited lectures presented at this meeting covering topics ranging from genetics, molecular mechanisms, pathophysiology, cardiovascular risk, to the management of patients with obesity-related hypertension. Stimulated by the continuing success of these Symposia, the organizers are currently planning to hold a Fourth International Symposium on Obesity and Hypertension (ISOH'05) in Berlin: a tentative date for this meeting has been set for 27–29, October 2005.International Journal of Obesity (2005) 29, 727–734. doi:10.1038/sj.ijo.0802946 Published online 12 April 2005 [ABSTRACT FROM AUTHOR]

Reviews several exhibitions, books and video and sound recordings related to electronic art. "Einsenstein: The Master's House," a biographical video featuring Russian film director Sergei Eisenstein; "Arranging Things: A Rhetoric of Object Placement," a book by Leonard Kohen; "Picturing Extraterrestrials: Alien Images in Modern Culture," a book written by John F. Moffitt; "Step Across the Border," an audio compact disc from Fred Records.

Overfeeding of rodents leads to increased local formation of angiotensin II due to increased secretion of angiotensinogen from adipocytes. Whereas angiotensin II promotes adipocyte growth and preadipocyte recruitment, increased secretion of angiotensinogen from adipocytes also directly contributes to the close relationship between adipose-tissue mass and blood pressure in mice. In contrast, angiotensin II acts as an antiadipogenic substance in human adipose tissue, and the total increase in adipose-tissue mass may be more important in determining human plasma angiotensinogen levels than changes within the single adipocyte. However, as increased local formation of angiotensin II in adipose tissue may be increased especially in obese hypertensive subjects, a contribution of the adipose-tissue renin–angiotensin system to the development of insulin resistance and hypertension is conceivable in humans, but not yet proven. Insulin resistance may be aggravated by the inhibition of preadipocyte recruitment, which results in the redistribution of triglycerides to the liver and skeletal muscle, and blood pressure may be influenced by local formation of angiotensin II in perivascular adipose tissue. Thus, although the mechanisms are still speculative, the beneficial effects of ACE-inhibition and angiotensin-receptor blockade on the development of type 2 diabetes in large clinical trials suggest a pathophysiological role of the adipose-tissue renin–angiotensin system in the metabolic syndrome. [Copyright &y& Elsevier]

Low plasma levels of the anti-inflammatory factor adiponectin characterize obesity and insulin resistance. To elucidate the relationship between plasma levels of adiponectin, adiponectin gene expression in adipose tissue, and markers of inflammation, we obtained blood samples, anthropometric measures, and subcutaneous adipose tissue samples from 65 postmenopausal healthy women. Adiponectin plasma levels and adipose-tissue gene expression were significantly lower in obese subjects and inversely correlated with obesity-associated variables, including high-sensitive C-reactive protein (hs-CRP) and interleukin-6 (IL-6). Despite adjustment for obesity-associated variables, plasma levels of adiponectin were significantly correlated to adiponectin gene expression (partial r = 0.38, P < 0.05). Furthermore, the inverse correlation between plasma levels of hs-CRP and plasma adiponectin remained significant despite correction for obesity-associated variables (partial r = -0.32, P < 0.05), whereas the inverse correlation between adiponectin plasma levels or adiponectin gene expression in adipose tissue with plasma IL-6 were largely dependent on the clustering of obesity-associated variables. In conclusion, our data suggest a transcriptional mechanism leading to decreased adiponectin plasma levels in obese women and demonstrate that low levels of adiponectin are associated with higher levels of hs-CRP and IL-6, two inflammatory mediators and markers of increased cardiovascular risk. [ABSTRACT FROM AUTHOR]

Recent studies suggest that angiotensin II (Ang II) plays a role in the adipogenesis of murine preadipocytes. Here, we examined the role of Ang II for the differentiation of primary cultured human preadipocytes. Preadipocytes were isolated from human adipose tissue and stimulated to differentiate. Quantitation of gene expression during adipogenesis was performed for renin-angiotensin system (RAS) genes. The influence of the RAS on adipogenic differentiation was investigated by addition of either angiotensinogen (AGT), Ang II, or angiotensin receptor antagonists to the differentiation medium. We also examined the influence of adipocytes on adipogenesis by co-culture experiments. Expression of the RAS genes AGT, renin, angiotensin-converting enzyme, and Ang II type 1 receptor increased during adipogenesis. Stimulation of the Ang II type 1 receptor by Ang II reduced adipose conversion, whereas blockade of this receptor markedly enhanced adipogenesis. Adipocytes were able to inhibit preadipocyte differentiation in the co-culture, and this effect was abolished by blockade of the Ang II type 1 receptor. This finding points to a functional role of the RAS in the differentiation of human adipose tissue. Because AGT secretion and Ang II generation are characteristic features of adipogenesis, we postulate a paracrine negative-feedback loop that inhibits further recruitment of preadipocytes by maturing adipocytes. [ABSTRACT FROM AUTHOR]