Hepatic Mitochondrial Renin-Angiotensin Systems

Introduction: The circulating renin-angiotensin system (RAS) was originally described as a key endocrine regulator of intravascular homeostasis; however, the existence of a local (tissue) RAS has become increasingly reported in a variety of tissues including liver. RAS components have now also been detected in rat heart, brain and smooth muscle cell mitochondria as well as within intramitochondrial dense bodies of rat adrenal tissue. Further, reduced RAS levels have been associated with improved endurance performance and fatigue resistance in human skeletal muscle, suggesting that low RAS activity is associated with metabolic efficiency, potentially via RAS action upon, or within, mitochondria. However, such investigation has often relied heavily upon qualitative techniques (e.g. Western blotting, immunofluorescence and electron microscopy), which contain inherent limitations in that they completely rely upon the limited specificity of antibodies to demonstrate the existence of intra-mitochondrial RAS components. Methods: The presence of RAS components within the mitochondria of rat hepatic tissue and liver cell-lines was investigated via sub-fractionation of rat liver tissue and cell-lines, followed by Western blotting, as well as via immunofluorescence and confocal microscopy, and electron microscopy. The mitochondrial effects of stimulating or antagonizing hepatic RAS were assessed via functional fluorescence microscopy (for assessment of NADH, calcium and mitochondrial membrane potential) and measurement of oxygen consumption within live cells of a liver cell-line. Results: Western blotting, immunofluorescence and electron microscopy suggested the presence of RAS components within mitochondria; however, there was a lack of results consistency between techniques and the staining patterns were largely non-specific. Western blotting further demonstrated the presence of a prominent 55 kDa band, when immunostaining a mitochondrial fraction with (angiotensin-converting enzyme) ACE Cterminal antibody (usual size 180 kDa). This was further explored via isolation of the 55 kDa molecule and mass spectrometry to yield results consistent with non-specific staining only. Addition of RAS agonists or antagonists to live liver cell-lines demonstrated no consistent results, except at supra-physiological levels, where RAS antagonists improved oxygen consumption. Conclusions: Such data suggest that the previous descriptions of RAS components within mitochondria are likely to be secondary to methodological flaws, particularly the reliance upon single antibodies, which have subsequently been shown to have poor specificity. Thus, the effect of ang II on liver mitochondria is unlikely to be direct and any such action is likely to occur via one of several intracellular pathways, regulation of gene expression or mitochondrial biogenesis

Visions Infernales: Characteristics of Style and Interpretation

Visions Infernales by the French composer Henri Sauguet is a song cycle for the bass voice with piano accompaniment set to a text by the twentieth-century poet, }fax Jacob. This composition, published in France in 1950, is contemporary in style with considerable dissonance, and therefore is probably not well known in this country. However, student and professional should become more familiar with the style characteristics and performance of modern repertoire

Exploring political risk in offshoring engagements

This research focuses on the analysis of political risk in the context of offshoring decisions. The study uses the Repertory Grid Technique, which entails a series of semi-structured interviews exploring key political risk experiences across offshoring engagements. The research extends the spectrum of political risk analysis in the context of offshoring engagements, and explores the varied impact of political risk across business activity types. The research identifies five key political risks affecting offshoring engagements and highlights the moderating effect of specific offshoring activity types Business Process Outsourcing, Information Technology Outsourcing or Knowledge Process Outsourcing on political risk implications. The research explores the conditioning effect of activity specific exposure to political risk and enhances the explanatory ability of the Transaction Cost Economics constructs, offering a novel operationalisation of the political risk component of external uncertainty. From a practical perspective, the research highlights the need for developing managerial tools to improve monitoring and identification of risks. The key practical contribution is the development of differentiated political risk typologies that can capture the nuances of external risks in offshoring, allowing for more accurate risk assessment of offshoring decisions

IUPUI Faculty Mentoring Exchange: A Platform to Seek and Volunteer Mentoring

poster abstractMentoring combines the impact of learning with the human need for social connection; it helps individuals achieve their best potential in a competitive and challenging world. Within educational organizations, people are willing to seek advice on various topics, including teaching, research, service, civic engagement, and mutual concerns. The IUPUI Faculty Mentoring Exchange is an application, which allows, faculty to seek mentoring, or offer to mentor to those who could benefit from their insights, expertise, and experience. The Mentoring Exchange delivers three core functionalities: 1.) Voluntary mentoring, 2.) A way to seek to mentor, and 3.) Establishing a social connection chain among the faculty from diverse departments and locations. Participating in the Mentoring Exchange is entirely voluntary. Users fill out a checklist to describe the types of insights and experience they wish to discuss with a colleague. The Mentoring Exchange will then offer a list of potential mentors who have described themselves as having such insights to offer. Then, it is up to the user to contact any of these colleagues and take it from there. Human-centered design processes were followed to deliver the system: user research, prototyping, implementation and iterative analysis. After observations and contextual inquiry, data was collected for sketching and prototyping. We learned about the types of mentoring faculty wish to seek out. Senior faculties were asked about their willingness to provide mentoring. Currently, we are evaluating what users are searching for with an ongoing collection of data. Next, we plan build intelligent social matchmaking ecosystem using machinelearning algorithm. Our work contributes to the enhancing of mentoring culture and creating social connections within the organization

Novel diagnostic and prognostic biomarkers in biliary tract cancer.

The worldwide incidence of biliary tract carcinoma (BTC, tumours of the bile ducts and gall-bladder) continues to rise, with the only potentially curative treatment remaining surgical resection or transplantation, possible in only a minority of patients. Late presentation and a paucity of effective treatments mandate the development of techniques for early lesion detection