Leptin fails to blunt the lipopolysaccharide-induced activation of the hypothalamic-pituitary-adrenal axis in rats

Copyright @ 2013 The authors. This work is licensed under a Creative Commons Attribution 3.0 Unported License.Obesity is a risk factor for sepsis morbidity and mortality, whereas the hypothalamic-pituitary-adrenal (HPA) axis plays a protective role in the body's defence against sepsis. Sepsis induces a profound systemic immune response and cytokines serve as excellent markers for sepsis as they act as mediators of the immune response. Evidence suggests that the adipokine leptin may play a pathogenic role in sepsis. Mouse endotoxaemic models present with elevated leptin levels and exogenously added leptin increased mortality whereas human septic patients have elevated circulating levels of the soluble leptin receptor (Ob-Re). Evidence suggests that leptin can inhibit the regulation of the HPA axis. Thus, leptin may suppress the HPA axis, impairing its protective role in sepsis.We hypothesised that leptin would attenuate the HPA axis response to sepsis.We investigated the direct effects of an i.p. injection of 2 mg/kg leptin on the HPA axis response to intraperitoneally injected 25 μg/kg lipopolysaccharide (LPS) in the male Wistar rat. We found that LPS potently activated the HPA axis, as shown by significantly increased plasma stress hormones, ACTH and corticosterone, and increased plasma interleukin 1β (IL1β) levels, 2 h after administration. Pre-treatment with leptin, 2 h before LPS administration, did not influence the HPA axis response to LPS. In turn, LPS did not affect plasma leptin levels. Our findings suggest that leptin does not influence HPA function or IL1b secretion in a rat model of LPS-induced sepsis, and thus that leptin is unlikely to be involved in the acute-phase endocrine response to bacterial infection in rats.The section is funded by grants from the MRC, BBSRC, NIHR and an Integrative Mammalian Biology (IMB) Capacity Building Award, and by a FP7-HEALTH-2009-241592 EuroCHIP grant and is supported by the NIHR Imperial Biomedical Research Centre Funding Scheme. This work is supported by a BBSRC Doctoral Training-Strategic Skills Award grant (BB/F017340/1)

Trends of Palestinian Higher Educational Institutions in Gaza Strip as Learning Organizations

The research aims to identify the trends of Palestinian higher educational institutions in Gaza Strip as learning organizations from the perspective of senior management in the Palestinian universities in Gaza Strip. The researchers used descriptive analytical approach and used the questionnaire as a tool for information gathering. The questionnaires were distributed to senior management in the Palestinian universities. The study population reached (344) employees in senior management is dispersed over (3) Palestinian universities. A stratified random sample of (182) employees from the Palestinian universities was selected and the recovery rate was (69.2%). Statistical analysis (SPSS) program was used for analysis and processing the data. The study found the following results: There is an agreement about: the importance of the focus of "organizational structure" with an average approval, the importance of "technological infrastructure" axis with high approval, and the importance of "strategic" with an average approval. The results concluded that the study sample agree on the importance of "organizational dimension" highly. The results showed that the sample believe that the "strategic leadership" level in the universities got medium-approval. There is a fair level agreement about the axis of interest "teams / committees". There is an agreement about the importance of the "human dimension" moderately. The results showed that the sample is highly agreed about the importance of focus of the "knowledge management", and the focus of the "continuing education". They agreed weakly to somewhat about the importance of the focus of "scientific research", moderately agree about the importance of the center of "institutional culture", agree moderately on the importance of "cognitive dimension". The results showed that the sample largely agree on the importance of the focus of "strategic partnerships and alliances". They agree highly on the axis "keep up with the labor market" and on the focus of the importance of "technology incubators". The results showed that the sample moderately agree about the importance of the theme on "consulting and training", the importance of the focus of "social responsibility", and the focus of the "Community dimension". The study found a group of recommendations including: there is a need to provide suitable environment that achieve learning organizations. There is a need to develop the technological infrastructure (hardware, software, networks, databases, and human skills) because of the great advantages that they offer. The universities need to adopt knowledge management in the academic and administrative departments because knowledge is the core of the work of these departments. The establishment of technology incubators in universities to adopt outstanding university research projects, to protect, to supports, and to market them; furthermore, to develop the capabilities and skills of employees in the field of information technology

The potential of the new EU Rural Development Programme in supporting Organic Farming

Background: In July 2004, the Commission presented a new proposal for a Council Regulation on support for rural development by the European Agricultural Fund for Rural Development (EAFRD) for the programming period 2007 – 2013 which has been agreed upon in June 2005 (European Commission 2005a, Council of the European Union 2005a and 2005b). The explanatory memorandum of the new Rural Development Programme (RDP) presented by the European Commission mentions that after a period of reforms of the First Pillar of the CAP, now focus will be led on the reform of rural development policy. However, this does not mean a paradigm shift but rather a consolidation and administrative simplification making rural development policy more efficient and coherent (Wehrheim 2005). Compared to current Council Regulation (EC) 1257/1999, the new RDP considers in Article 6 to strengthen the partnership approach through close consultation of competent regional, local and other public authorities as well as Non-governmental organisations and private bodies representing civil society (European Commission 2004b). The regulation seeks dovetailing policies of first and second pillar: e.g. through modulation. On the other side, EU rural development policy should move towards a more strategic approach, reinforcing it and simplifying its implementation (European Commission, 2004a). To ensure the sustainable development of rural areas, the new RDP focuses on a limited number of core priority objectives relating to agriculture and forestry (European Commission, 2004b): 1. improving the competitiveness of agriculture and forestry by means of support for restructuring, development and innovation 2. improving the environment and the countryside by means of support for land management 3. improving the quality of life in rural areas and encouraging diversification of economic activity: Each of these core objectives relates to one thematic axis for which each a range of measures are proposed: Axis 1: Improving the competitiveness of the agriculture and forestry sector Axis 2: Improving the environment and the countryside Axis 3: The quality of life in rural areas and diversification of the rural economy In addition a fourth overarching axis is introduced which relates to all three objectives: Axis 4: “LEADER” Axis While so far the 2nd Pillar of the CAP was funded by two different financial sources (EAGGF Guidance and Guarantee section), the new regulation envisages the creation of only one new fund for Pillar 2: The European Agricultural Fund for Rural Development (EAFRD). Thus, current differences of Guidance and Guarantee section as concerns programming, administration and monitoring will be dispensed, which might lead to a significant ease of administrative tasks (Grajewski 2004). The resources available for the period 2007 to 2013 amount according to Article 70 of the Council proposal to 88,75 billion Euro at constant 2004 prices (European Council, 2005). The minimum EU fund contribution at axis level shall be 20%. In the case of Axis 1 and 3, maximum funds are ceiled to 50% of the eligible public expenditures (75% in convergence regions). For Axis 2 and the Leader Axis the maximum rate will be 55% (80% in convergence regions), expressing the EU priority attached to these axes. For the outermost regions the maximum co-financing rates are increased by 5 points (Council of the European Union 2005a). The implementation process of the new policy foresees adoption of the Community level strategic guidelines for rural development by autumn 2005 in order to enable Member states to finalise their national strategic plans until mid 2006 (European Commission 2005a). So far, there has only been some scientific discussion on earlier stages of the respective regulation (Grajewski et al. 2004, Schader and Stolze 2005, Wissenschaftlicher Beirat Agrarpolitik, nachhaltige Landbewirtschaftung und Entwicklung ländlicher Räume beim Bundesministerium für Verbraucherschutz, Ernährung und Landwirtschaft 2005). Generally the approach of the regulation was considered to be an improvement. However, little reference has been made so far in the discussion to the prospects the new policy holds for support of organic farming, inspite of the fact that there are economic arguments in favour of support for organic farming (Dabbert et al. 2004). Organic farming is mentioned only once in the regulation, as a minor point and without any specifics. This seems to be in contrast to the importance given to organic farming by other statements of the Commission (European Commission 2004c). Also the recent Commission proposal for strategic guidelines (European Commission 2005b) is more explicit on the role of organic farming for rural development. It thus seems worthwhile to take a closer look at this aspect

Nilai Strategis Indian Ocean Rim Association Bagi Indonesia Dalam Penerepan Poros Maritim Tahun 2015

Since Joko Widodo inaugurated as the President of Indonesia, Indonesia made a movement of the policy based on Maritime Axis concept. The concept means to recalling the nature of Indonesia's paradigm in case of the nation is the archipelagic state. In the process of the implementation of the concept, particularly on 2015 October, Indonesia officially became the chairman of Indian Ocean Rim Association (IORA). The implementation of Maritime Axis had politically aided by these two correlated entities.This research is a descriptive-analytic that aims to explain the strategic values of IORA and theoretically using Regional Security Complex Theory by Barry Buzan that describes the complexity in a region. In realism realm, the RSCT is utilized to as one of substructure and has role in theoretical precisely in International system case.The equilibrium of Maritime Axis Pilar and 6 Priorities of IORA concluded that IORA has strategic values in implementing Maritime Axis concept for Indonesia. The statement hypothetically supports by several reasons such as Indonesia could use IORA for rebuilding the maritime culture, guarding the sea resources, maritime diplomacy, and building the maritime power that accumulated by three realms such as political and security, economy, and socio-cultural

Remarks on Boston Consulting Group Method (BCG)

The situational plan of an enterprise in the market can be determined by means of the BCG method. The analysis consists in graphical presentation of the spatial distribution of the enterprise activity conditions. The presentation is made in two dimensional spaces in which horizontal axis represents the relative participation of the strategic units in the market and vertical axis represents the market growth rate. In such a coordinate system, enterprise activity can be visualized by means of the circles. In the paper a proposition has been put forward how to calculate the estimators of coordinates of circle centers and their radii in BCG method, taking into consideration the assessment errors on the axis of relative participation of the strategic unit under study in the market and on the axis of market’s growth rate. Advantage has been taken of the general case of LSE including Lagrange’s multipliers method with nonlinear constrains equations. An example illustrating the method proposed has been included.BGG method, estimator, situation plan, prognosing

Supply chain management as the key to a firm’s strategy in the global marketplace

Purpose: This research aims to analyze the intersection of two literature streams: that of strategy and supply chain management (SCM). This review should create a better understanding of “strategic SCM” by focusing on relevant theories in the strategic management field and their intersection with SCM to develop a joint research agenda. Design/Methodology/Approach: We conducted a correspondence analysis on the content of 3,402 articles from the top SCM journals. This analysis provides a map of the intellectual structure of content in this field to date. The key trends and changes were identified in strategic SCM research from 1990-2014 as well as the intersection with the key schools of strategic management. Findings: The results suggest that SCM is key to a successful deployment of strategy for competing in the global marketplace. The main theoretical foundations for research in this field were identified and discussed. Gaps were detected and combinations of theoretical foundations of strategic management and SCM suggest four poles for future research: agents and focal firm; distributions and logistics strategic models; SCM competitive requirements; SCM relational governance. Research limitations/implications: Scholars in both the strategy and the SCM fields continue to search for competitive advantages. Much recent research indicates that strategic SCM can be a critical source for that advantage. One of the limitations of our research is that the analysis does not include every journal that published an article mentioning SCM. However, the 34 journals selected are reputed to be the most influential on SCM and focused primarily on SCM. Practical implications: The map of the intellectual structure of research to strategic SCM highlights the need to combine different theoretical approaches to the complex phenomenon of SCM. Practitioners should consider the supply chain as an informal organization and should devote time and resources to build a shared advantage across the supply chain. They should also consider the inherent benefits and risks that sharing Originality/value: The paper demonstrates that strategic SCM needs a balanced and rigorous combination of theoretical approaches to deliver more theory-driven evidences. Our research combines both a qualitative analysis and a quantitative methodology that summarizes gaps and then outlines future research from a large sample of articles. This methodology is an original contribution to this field and offers some assistance for enlarging the sample of future literature reviews

Strategic Targeting Of The PI3k–NFκB Axis In Cisplatin-resistant NSCLC

Chemoresistance is a major therapeutic challenge to overcome in NSCLC, in order to improve the current survival rates of <15% at 5 years. We and others have shown increased PI3K signaling in NSCLC to be associated with a more aggressive disease, and a poorer prognosis. In this study, targeted inhibition of three strategic points of the PI3K–NFκB axis was performed with the aim of exploiting vulnerabilities in cisplatin-resistant NSCLC cells. Cisplatin-resistant cell lines were previously generated through prolonged exposure to the drug. Expression of PI3K and NFκB pathway-related genes were compared between cisplatin-resistant cells and their matched parent cells using a gene expression array, qRT-PCR, DNA sequencing, western blot, and immunofluorescence. Targeted inhibition was performed using GDC-0980, a dual PI3K–mTOR inhibitor currently in Phase II clinical trials in NSCLC, and DHMEQ, an inhibitor of NFκB translocation which has been used extensively both in vitro and in vivo. Effects of the two inhibitors were assessed by BrdU proliferation assay and multiparameter viability assay. NFKBIA was shown to be 12-fold overexpressed in cisplatin-resistant cells, with no mutations present in exons 3, 4, or 5 of the gene. Corresponding overexpression of IκBα was also observed. Treatment with DHMEQ (but not GDC-0980) led to significantly enhanced effects on viability and proliferation in cisplatin-resistant cells compared with parent cells. We conclude that NFκB inhibition represents a more promising strategy than PI3K–mTOR inhibition for treatment in the chemoresistance setting in NSCLC