Contribution of outgrowth endothelial cells from human peripheral blood on in vivo vascularization of bone tissue engineered constructs based on starch polycaprolactone scaffolds

In the present study we assessed the potential of human outgrowth endothelial cells (OEC), a subpopulation within endothelial progenitor cell cultures, to support the vascularization of a complex tissue engineered construct for bone. OEC cultured on starch polycaprolactone fiber meshes (SPCL) in monoculture retained their endothelial functionality and responded to angiogenic stimulation by VEGF (vascular endothelial growth factor) in fibrin gel-assays in vitro. Co-culture of OEC with human primary osteoblasts (pOB) on SPCL, induced an angiogenic activation of OEC towards microvessel-like structures achieved without additional supplementation with angiogenic growth factors. Effects of co-cultures with pOB on the vascularization process by OEC in vivo were tested by subcutaneous implantation of Matrigel! plugs containing both, OEC and pOB, and resulted in OEC-derived blood vessels integrated into the host tissue and anastomosed to the vascular supply. In addition, morphometric analysis of the vascularization process by OEC indicated a better performance of OEC in the co-cultures with primary osteoblasts compared to monocultures of OEC. The contribution of OEC to vascular structures and the beneficial effect of the co-culture with primary human osteoblasts on the vascularization in vivo was additionally proven by subcutaneous implantation of pre-cellularized and pre-cultured SPCL constructs. OEC contributed to the vascular structures, by generating autogenic vessels or by incorporation into chimeric vessels consisting of both, human and mouse endothelial cells. The current data highlight the vasculogenic potential of OEC for bone tissue engineering applications and indicate a beneficial influence of constructs including both osteoblasts and endothelial cells for vascularization strategies.The authors would like to thank B. Malenica, C. Braun, L. Meyer, K. Molter, M. Muller. J. Alonso-Monje for their excellent technical assistance. This work was financially supported by grants from the European commission (HIPPOCRATES N degrees NMP3-CT-2003-505758; EXPERTISSUES Contract nr.: 500283-2) and BMBF-Grant for German-Chinese Cooperation in Regenerative Medicine (grant number 0315033)

Restoring Akt1 activity in outgrowth endothelial cells from south asian men rescues vascular reparative potential

Recent data suggest reduced indices of vascular repair in South Asian men, a group at increased risk of cardiovascular events. Outgrowth endothelial cells (OEC) represent an attractive tool to study vascular repair in humans and may offer potential in cell-based repair therapies. We aimed to define and manipulate potential mechanisms of impaired vascular repair in South Asian (SA) men. In vitro and in vivo assays of vascular repair and angiogenesis were performed using OEC derived from SA men and matched European controls, prior defining potentially causal molecular mechanisms. SA OEC exhibited impaired colony formation, migration, and in vitro angiogenesis, associated with decreased expression of the proangiogenic molecules Akt1 and endothelial nitric oxide synthase (eNOS). Transfusion of European OEC into immunodeficient mice after wire-induced femoral artery injury augmented reendothelialization, in contrast with SA OEC and vehicle; SA OEC also failed to promote angiogenesis after induction of hind limb ischemia. Expression of constitutively active Akt1 (E17KAkt), but not green fluorescent protein control, in SA OEC increased in vitro angiogenesis, which was abrogated by a NOS antagonist. Moreover, E17KAkt expressing SA OEC promoted re-endothelialization of wire-injured femoral arteries, and perfusion recovery of ischemic limbs, to a magnitude comparable with nonmanipulated European OEC. Silencing Akt1 in European OEC recapitulated the functional deficits noted in SA OEC. Reduced signaling via the Akt/eNOS axis is causally linked with impaired OEC-mediated vascular repair in South Asian men. These data prove the principle of rescuing marked reparative dysfunction in OEC derived from these men.This work was supported by the British Heart Foundation, London, UK, and the Diabetes Research and Wellness Foundation, Portsmouth, UK

S = 3 Ground State for a Tetranuclear Mn^(IV)₄O₄ Complex Mimicking the S₃ State of the Oxygen Evolving Complex

The S₃ state is currently the last observable intermediate prior to O–O bond formation at the oxygen-evolving complex (OEC) of Photosystem II, and its electronic structure has been assigned to a homovalent Mn^(IV)₄ core with an S = 3 ground state. While structural interpretations based on the EPR spectroscopic features of the S₃ state provide valuable mechanistic insight, corresponding synthetic and spectroscopic studies on tetranuclear complexes mirroring the Mn oxidation states of the S₃ state remain rare. Herein, we report the synthesis and characterization by XAS and multifrequency EPR spectroscopy of a Mn^(IV)₄O₄ cuboidal complex as a spectroscopic model of the S₃ state. Results show that this Mn^(IV)₄O₄ complex has an S = 3 ground state with isotropic ⁵⁵Mn hyperfine coupling constants of −75, −88, −91, and 66 MHz. These parameters are consistent with an αααβ spin topology approaching the trimer–monomer magnetic coupling model of pseudo-octahedral Mn^(IV) centers. Importantly, the spin ground state changes from S = 1/2 to S = 3 as the OEC is oxidized from the S₂ state to the S₃ state. This same spin state change is observed following oxidation of the previously reported Mn^(III)Mn^(IV)₃O₄ cuboidal complex to the Mn^(IV)₄O₄ complex described here. This sets a synthetic precedent for the observed low-spin to high-spin conversion in the OEC

Geographical Risk of Money Laundering in the European Banking System

The issue of risk of money laundering in the European banking system was presented in the article. It describes two approaches used by regulators to prevent the mentioned phenomenon: the rule-based approach and the risk-based approach. The author also identified strategies which are used by banks as entities functioning to maximize profit in the conditions of having full and incomplete information by the FIU. Then, the European countries were analyzed with respect to participating reports on suspicious transactions in the total number of reports, which are sent by all the obligated entities to the national financial intelligence units. We also verified the value of two indicators: the value of above-threshold transactions and the value of financial penalties, which are imposed on banks for failure to comply with the rules on anti-money laundering. Some hypotheses were examined. With the increase in GDP per capita grows the maximum value of the mentioned financial penalties grows. There is a negative correlation between the share of banks in the total of reported suspicious transactions and GDP per capita, which is an effect of extending the list of the obligated entities and the lack of the differentiation of sanctions in the various categories of such entities. In connection with the applying of transitional period for implementing the directive by the banks, there is an inverse relationship between the amount of the penalty, and the number of suspicious transactions reports

Modern Theories of Regional Development – a Review of Some Concepts

Researches on determinants of regional development are an important part of economic thought. And just like the whole economic theory, it was the subject of visible evolution as the whole economy had changed and as we gained some practice in stimulating economic development. However, in the public awareness one can still observe a strong influence of “old” or traditional theories. Many (also some economists) still see regional development as an exogenous process which should be inspired and managed by a central government. Also, there is a strong tendency to consider the main goal of regional policy as artificial leveling of regions’ development. Only recently there has been a visible shift in the approach to the problem of regional development. The aim of the article is to present some most commonly recognized modern theories of regional development, which stand opposite to the traditional approach. It shows the evolution of theories of regional development from exogenous to endogenous concepts, and from the sectoral to holistic view on this issue. Of course, it does not cover all of the thoughts of a fruitful discussion on this topic. It is rather an inspiration to increase and improve one’s knowledge of this topic

E2F5 status significantly improves malignancy diagnosis of epithelial ovarian cancer

<p>Abstract</p> <p>Background</p> <p>Ovarian epithelial cancer (OEC) usually presents in the later stages of the disease. Factors, especially those associated with cell-cycle genes, affecting the genesis and tumour progression for ovarian cancer are largely unknown. We hypothesized that over-expressed transcription factors (TFs), as well as those that are driving the expression of the OEC over-expressed genes, could be the key for OEC genesis and potentially useful tissue and serum markers for malignancy associated with OEC.</p> <p>Methods</p> <p>Using a combination of computational (selection of candidate TF markers and malignancy prediction) and experimental approaches (tissue microarray and western blotting on patient samples) we identified and evaluated E2F5 transcription factor involved in cell proliferation, as a promising candidate regulatory target in early stage disease. Our hypothesis was supported by our tissue array experiments that showed E2F5 expression only in OEC samples but not in normal and benign tissues, and by significantly positively biased expression in serum samples done using western blotting studies.</p> <p>Results</p> <p>Analysis of clinical cases shows that of the E2F5 status is characteristic for a different population group than one covered by CA125, a conventional OEC biomarker. E2F5 used in different combinations with CA125 for distinguishing malignant cyst from benign cyst shows that the presence of CA125 or E2F5 increases sensitivity of OEC detection to 97.9% (an increase from 87.5% if only CA125 is used) and, more importantly, the presence of both CA125 and E2F5 increases specificity of OEC to 72.5% (an increase from 55% if only CA125 is used). This significantly improved accuracy suggests possibility of an improved diagnostics of OEC. Furthermore, detection of malignancy status in 86 cases (38 benign, 48 early and late OEC) shows that the use of E2F5 status in combination with other clinical characteristics allows for an improved detection of malignant cases with sensitivity, specificity, F-measure and accuracy of 97.92%, 97.37%, 97.92% and 97.67%, respectively.</p> <p>Conclusions</p> <p>Overall, our findings, in addition to opening a realistic possibility for improved OEC diagnosis, provide an indirect evidence that a cell-cycle regulatory protein E2F5 might play a significant role in OEC pathogenesis.</p

Conceptual development of ethical climate and its impacts on individuals and organizations

Aksoy, Seval (Dogus Author)“Örgütsel Etik İklim (ÖEİ)” kavramı özellikle 2000’li yıllarda üzerinde fazlasıyla araştırma yapılmış olan bir örgütsel davranış çalışma konusudur. Yapılan bu çalışmada, ÖEİ’nin örgütsel özdeşleşme (ÖÖ), örgütsel bağlılık (ÖB) ve kişiörgüt uyumu (KÖU) kavramlarıyla olan ilişkileri, Kocaeli’nde faaliyet göstermekte olan imalat firmalarında yapılan bir uygulamalı çalışma ile test edilmiştir. Analiz sonuçlarına göre, ÖEİ ile ÖÖ ve ÖB arasında pozitif ilişkinin bulunduğu, ayrıca ÖEİ ile ÖB ve ÖÖ arasındaki ilişkide KÖU’nun kısmi ara değişken rolü oynadığı tespit edilmiştir.The concept of “Organizational Ethical Climate (OEC)” is a subject matter of organizational attitude research study on which many researchers have been conducted so far, especially after 2000’s. In this research, relationships among OEC and organizational identification (OI), commitment (OC) and personorganization fit (POF) are analyzed through an empirical research conducted in manufacturing firms located in Kocaeli. Results indicate that there are positive relationships between OEC and OI, as well as OEC and OC, also POF mediates the relationships between OEC and OI / OC

Development of Banking Sectors in Kosovo and Montenegro in the Years 2000-2010

The article presents main aspects of the development of banking markets in two Balkan countries – Kosovo and Montenegro. Both of them are charaterised by similar recent history, both in political and economical fields. Their financial sectors had to be built almost from scratch. The author describes the stages of development of competition in the banking sectors, using the following ratios: performace, structure, liquidity. The data is based on the information achieved from Kosovar and Montenegral central banks. Comparison of their achievements are presented on the pentagon adopted from macroeconomy stability pentagon, introduced in Poland by Institute for Market, Consumption and Business Cycles Research. The long way from centrally planned economy to market economy, in both countries, in both political and financial aspects has resulted in a successful transformation. The growing economic strength in Kosovo and Montenegro will allow their financial institutions to improve their performance and expand their activities in the future

The Implementation of Synthetic Variable for Constructing the Sandard of Living Measure in European Union Countries

This paper proposes the use of synthetic variable to examine differences in the standard of living in the EU countries. The synthetic variable allows to replace the whole set of variables into one aggregated variable. This variable is the basis for organizing and grouping countries in terms of standard of living. The subject of empirical analysis are 24 member states of the European Union in 1995-2010. The analysis of synthetic variable reveals that there are significant disparities between countries in the field of overall socio-economic development. The analysis show favorable situation in Ireland and very unfavorable conditions in Romania, Bulgaria and the Baltic countries

Hyaluronan and Hyaluronidase, which is better for embryo development?

Our aim was to examine size-specific effects of Hyaluronan (HA) on preimplantation embryo development. We investigated the effects of Hyalovet (HA, 500–750 kDa; the size produced by HA synthase-3, which is abundant in the oviduct), or HA treated with Hyaluronidase-2 (Hyal2; also expressed in the oviduct that breaks down HA into 20 kDa fragments). In experiment 1 (in vivo), oviducts of synchronized and superovulated ewes (n = 20) were surgically exposed on Day 2 post-mating, ligated, and infused with either Hyalovet, Hyalovet + Hyal2, Hyal2, or PBS (control). Ewes were killed 5 days later for recovery of embryos and oviductal epithelial cells (OEC). Blastocyst rates were significantly higher in Hyal2 and Hyalovet + Hyal2 oviducts. Hyaluronidase-2 infusion resulted in higher blastocyst cell numbers and hatching rates. This was associated with increased HSP70 expression in OEC. In contrast, Hyalovet resulted in the lowest development to blastocyst stage and lowest hatching rates, and decreased IGF2 and IGFBP2 expression in OEC. IGF1 and IL1α expression were not affected. In experiment 2, to rule out indirect effects of oviductal factors, ovine embryos were produced and cultured with the same treatments in vitro from Day 2 to 8. Hyaluronidase-2, but not Hyalovet, enhanced blastocyst formation and reduced inner cell mass apoptosis. Hyalovet inhibited hatching. In conclusion, the presence of large-size HA (500–750 kDa) in the vicinity of developing embryos appears to disturb the oviductal environment and embryo development in vivo and in vitro. In contrast, we show evidence that breakdown of HA into smaller fragments is required to maximize embryo development and blastocyst quality