237 research outputs found
Women in leadership program 1993: shaping the culture
In discussing Women in Leadelrship one member of the Management Group sometimes used the term Program , and sometimes Project . This was not a mere slip of the tongue. One useful way to conceptualise Women in Leadership is as a Project- which seeks to strategically engage with a changing institution, and which is both organic and structured. Part of the Project structure is the Program. The Program is made up of three formal elements: The Collegial Groups; the Public Lecture Series and the National Conference. And yet, part of the Purpose of the Program is to engage with, shape and respond to changes in the structure and culture of Edith Cowan University - so the distinction is no more than arbitrary. In this report, Program refers to the three formal elements; Project refers to the wider elements- Women in Leadership is used to denote the Program in the context of the wider elements.
Undertaking an evaluation for a client with a successful program should have been the easiest of evaluation tasks. Grappling with the parameters of the Program , and clearly characterising what the Project is, made the task more complex.
Evaluation of a program as innovative as Women in Leade1·ship has raised challenges to the standard criteria of what constitutes evaluation. An evaluation which simply tests the extent to which the Program has met its objectives, as set out in the Funding Application (see Appendix 1), would exclude or marginalise much of what Women in Leadel\u27ship is about .
Over the course of this evaluation, it became clear that the crucial element of Women in Leadel\u27ship is the paradigm of leadership upon which the Project is based. This raises challenges for identifying specific evaluation criteria. How to evaluate a paradigm, or a Project such as Women in Leadel\u27ship, which is directed at long term cultural change? Further, in an institution undergoing rapid changes, causalities are difficult to untangle.
The extent to which Women in Leadership is the causal factor in the discernible changes in the structure and culture of Edith Cowan University is and will continue to be debated. This debate encourages reflection about the structure of Edith Cowan University and is in itself a catalyst for change. This is a 1·elevant evaluative criterion, given the long term nature of the Project
The paraventricular nucleus and heart failure
What is the topic of this review? This review gives an update on the cellular and molecular mechanisms within the autonomic nervous system involved in non‐pathological and pathological cardiovascular regulation. What advances does it highlight? For cardiovascular homeostasis in non‐pathological conditions to be maintained, discrete neural networks using specified signalling mechanisms at both cellular and molecular levels are required. In heart failure, the cell signalling protein partners CAPON and PIN decrease the bioavailability of nitric oxide by inhibiting neuronal nitric oxide synthase activity, leading to the removal of tonic neuronal inhibition. Following a myocardial infarction, pro‐inflammatory cytokines in the paraventricular nucleus and the subsequent generation of reactive oxygen species, via angiotensin II activation of the angiotensin II type 1 receptor, increase neuronal excitability further, leading to sympathetic excitation. A pathological feature of heart failure is abnormal control of the sympathetic nervous system. The paraventricular nucleus of the hypothalamus (PVN) is one of the most important central sites involved in regulating sympathetic tone and is, in part, responsible for the dysregulation of the sympathetic nervous system evident in heart failure. Generation of sympathetic tone in response to fluctuations in cardiovascular regulation uses discrete anatomical pathways and neurochemical modulators. Direct and indirect projections from the PVN pre‐autonomic neurons innervate the sympathetic preganglionic neurons in the spinal cord, which in turn innervate sympathetic ganglia that give rise to the sympathetic nerves. Pre‐autonomic neurons of the PVN themselves receive an afferent input arising from the nucleus tractus solitarii, and viscerosensory receptors convey cardiovascular fluctuations to the nucleus tractus solitarii. The PVN contains excitatory and inhibitory neurons, whose balance determines the sympathetic tone. In non‐pathological conditions, the tonic inhibition of the PVN pre‐autonomic neurons is mediated by GABA‐ and NO‐releasing neurons. In heart failure, the pre‐autonomic neurons are disinhibited by the actions of the excitatory neurotransmitters glutamate and angiotensin II, leading to increased sympathetic activity. A key feature of the disinhibition is a reduction in the bioavailability of NO as a consequence of disrupted CAPON and PIN signalling mechanisms within the neuron. Another critical feature that contributes to increased neuronal excitation within the PVN is the production of pro‐inflammatory cytokines immediately following a myocardial infarction, the activation of the angiotensin II type 1 receptor and the production of reactive oxygen species. By examining the changes associated with the sympathetic nervous system pathway, we will progress our understanding of sympathetic regulation in heart failure, identify gaps in our knowledge and suggest new therapeutic strategies
The chronic and acute effects of (poly)phenols on sucrase isomaltase using the Caco-2/TC7 cell model
Evidence from animal models and human intervention studies indicates that polyphenols can potentially attenuate the postprandial glycaemic response by inhibition of α-glucosidases, critical for carbohydrate digestion, and by attenuation of monosaccharide transport across small intestinal enterocytes. Therefore, this study evaluated the effect of polyphenols, including an oleuropein-rich olive leaf extract, on sucrose hydrolysis and transport. Controlling the glycaemic response reduces the risk of development and progression of type 2 diabetes, much like the anti-diabetic drug acarbose. An in vitro inhibition assay for sucrase and maltase activity was optimised using Caco-2/TC7 cells as a human enzyme source and compared to a rat enzyme. Inhibitors were more effective on human compared to rat sucrase while the reverse was true for maltase. Chronic sucrose exposure led to altered N- and O-glycosylation and the sucrase Km increased by 15% compared to cells cultured in glucose. A chronic 3-day treatment with 1.5 mg/mL olive leaf extract reduced the sucrase specific activity by 31% and 26% for cells cultured in glucose and sucrose, respectively. Sucrase N-glycosylation increased in cells cultured in sucrose and this could have led to the decrease in Km. Oleuropein treatment decreased cell surface sucrase by 41% when cultured long-term in glucose but not sucrose. Transport studies for glucose-cultured cells showed that chronic treatment reduced sucrase hydrolysis and attenuated of fructose transport and GLUT2-mediated glucose transport. These results show for the first time that chronic treatment with olive polyphenols can reduce the sucrose hydrolysis and modulate glucose and fructose transport. Changes in post-translational modifications of sucrase with different treatments opens up new areas of research. Investigations are warranted regarding the use of olive leaf extract in humans for glycaemic control after sugar consumption with the suggestion that sugar intake might impact the effectiveness of the treatment
Electrophysiological characterisation of atrial volume receptors using ex‐vivo models of isolated rat cardiac atria
Atrial volume receptors are a family of afferent neurons whose mechanically sensitive endings terminate in the atria, particularly at the cavo‐atrial junctions. These mechanosensors form the afferent limb of an atrial volume receptor reflex which regulates plasma volume. The prevailing functional classification of atrial receptors arose as a result of in‐vivo recordings in the cat and dog and were classified as type A, B or intermediate according to the timing of peak discharge during the cardiac cycle. In contrast, there have been far fewer studies of the common small laboratory mammals such as the rat. Using several ex‐vivo rat cavo‐atrial preparations, a total of 30 successful single cavo‐atrial mechanosensory recordings were obtained. These experiments show that the rat possesses type A, B and intermediate atrial mechanoreceptors as described for larger mammals. Recording these cavo‐atrial receptors proved challenging from the main vagus but direct recording from the cardiac vagal branch greatly increased the yield of mechanically sensitive single units. In contrast to type A units, type B atrial mechanoreceptor activity was never observed at room temperature but required elevation of temperature to a more physiological range in order to be detected. The adequate stimulus for these receptors remains unclear however, type A atrial receptors appear insensitive to direct atrial stretch when applied using a programmable positioner. The findings suggest that type A and type B atrial receptors utilise different molecular transduction mechanisms
Nutritional implications of olives and sugar: attenuation of post-prandial glucose spikes in healthy volunteers by inhibition of sucrose hydrolysis and glucose transport by oleuropein
Purpose: The secoiridoid oleuropein, as found in olives and olive leaves, modulates some biomarkers of diabetes risk in vivo. A possible mechanism may be to attenuate sugar digestion and absorption.
Methods: We explored the potential of oleuropein, prepared from olive leaves in a water soluble form (OLE), to inhibit digestive enzymes (α-amylase, maltase, sucrase), and lower [¹⁴C(U)]-glucose uptake in Xenopus oocytes expressing human GLUT2 and [¹⁴C(U)]-glucose transport across differentiated Caco-2 cell monolayers. We conducted 7 separate crossover, controlled, randomised intervention studies on healthy volunteers (double-blinded and placebo-controlled for the OLE supplement) to assess the effect of OLE on post-prandial blood glucose after consumption of bread, glucose or sucrose.
Results: OLE inhibited intestinal maltase, human sucrase, glucose transport across Caco-2 monolayers, and uptake of glucose by GLUT2 in Xenopus oocytes, but was a weak inhibitor of human α-amylase. OLE, in capsules, in solution or as naturally present in olives, did not affect post-prandial glucose derived from bread, while OLE in solution attenuated post-prandial blood glucose after consumption of 25 g sucrose, but had no effect when consumed with 50 g of sucrose or glucose.
Conclusion: The combined inhibition of sucrase activity and of glucose transport observed in vitro was sufficient to modify digestion of low doses of sucrose in healthy volunteers. In comparison, the weak inhibition of α-amylase by OLE was not enough to modify blood sugar when consumed with a starch-rich food, suggesting that a threshold potency is required for inhibition of digestive enzymes in order to translate into in vivo effects
Inhibition of Human and Rat Sucrase and Maltase Activities To Assess Antiglycemic Potential: Optimization of the Assay Using Acarbose and Polyphenols
We optimized the assays used to measure inhibition of rat and human α-glucosidases (sucrase and maltase activities), intestinal enzymes which catalyze the final steps of carbohydrate digestion. Cell-free extracts from fully differentiated intestinal Caco-2/TC7 monolayers were shown to be a suitable source of sucrase–isomaltase, with the same sequence as human small intestine, and were compared to a rat intestinal extract. The kinetic conditions of the assay were optimized, including comparison of enzymatic and chromatographic methods to detect the monosaccharide products. Human sucrase activity was more susceptible than the rat enzyme to inhibition by acarbose (IC₅₀ (concentration required for 50% inhibition) = 2.5 ± 0.5 and 12.3 ± 0.6 μM, respectively), by a polyphenol-rich green tea extract, and by pure (−)-epigallocatechin gallate (EGCG) (IC₅₀ = 657 ± 150 and 950 ± 86 μM respectively). In contrast, the reverse was observed when assessing maltase activity (e.g., EGCG: IC₅₀ = 677 ± 241 and 14.0 ± 2.0 μM for human and rat maltase, respectively). 5-Caffeoylquinic acid did not significantly inhibit maltase and was only a very weak inhibitor of sucrase. The data show that for sucrase and maltase activities, inhibition patterns of rat and human enzymes are generally qualitatively similar but can be quantitatively different
The atypical 'hippocampal' glutamate receptor coupled to phospholipase D that controls stretch-sensitivity in primary mechanosensory nerve endings is homomeric purely metabotropic GluK2
ACKNOWLEDGEMENTS We would like to thank: Prof. Christophe Mulle, University of Bordeaux, France for the generous donation of the GluK2-Neo mice; Prof. Roberto Pellicciari and Prof. Maura Marinozzi, University of Perugia, Italy for the generous gift of PCCG-13; the Microscopy and Histology core facility at the Institute of Medical Sciences, University of Aberdeen for their support and assistance in some of the imaging in this work. We would also like to thank Prof. Gernot Riedel, University of Aberdeen UK and Prof. David Jane, University of Bristol UK for helpful comments during the work and discussion about drafts of this manuscript.Peer reviewedPublisher PD
Hypothalamic paraventricular nucleus neuronal nitric oxide synthase activity is a major determinant of renal sympathetic discharge in conscious Wistar rats
Pull-out behaviour of glass-fibre reinforced polymer perforated plate connectors embedded in concrete. Part II: Prediction of load carrying capacity
The authors have recently proposed an innovative connector system that consists on a Glass Fibre Reinforced Polymer (GFRP) perforated plate that is embedded into Steel Fibre Reinforced Self Compacting Concrete (SFRSCC) layers. The connection is strongly based in the mechanical interlock assured by the dowels originated from the SFRSCC passing through the holes opened on the GFRP plates. In this study, an analytical framework to evaluate the load capacity of the connections when loaded transversally was developed based on experimental pull-out tests presented in the companion paper (Part I). For a better understanding of the mechanical behaviour of the connections and to allow to make estimations of the load capacity of connection when it is conditioned by the rupture of the connector itself, pull-out pin-bearing tests with single-hole plates were executed to assess the effect of the type of GFRP on the strain distribution in the vicinity of the holes until the failure, as well as the estimated failure modes and load capacities of the connections.- This work is part of the research project QREN number 5387, LEGOUSE, involving the companies Mota-Engil, CiviTest, the ISISE/University of Minho and PIEP. The first author would like to thank the financial support provided by PAIP/UNILA. The second author wish to acknowledge the grant SFRH/BSAB/114302/2016 provided by FCT.info:eu-repo/semantics/publishedVersio
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