Diabetic cardiomyopathy and post-infarct ventricular remodelling : Effects of levosimendan in a rodent model of type II diabetes

Type 2 diabetes is a risk factor for the development of cardiovascular disease. Recently, the term diabetic cardiomyopathy has been proposed to describe the changes in the heart that occur in response to chronic hyperglycemia and insulin resistance. Ventricular remodelling in diabetic cardiomyopathy includes left ventricular hypertrophy, increased interstitial fibrosis, apoptosis and diastolic dysfunction. Mechanisms behind these changes are increased oxidative stress and renin-angiotensin system activation. The diabetic Goto-Kakizaki rat is a non-obese model of type 2 diabetes that exhibits defective insulin signalling. Recently two interconnected stress response pathways have been discovered that link insulin signalling, longevity, apoptosis and cardiomyocyte hypertrophy. The insulin-receptor PI3K/Ak pathway inhibits proapoptotic FOXO3a in response to insulin signalling and the nuclear Sirt1 deacetylase inhibits proapoptotic p53 and modulates FOXO3a in favour of survival and growth. --- Levosimendan is a calcium sensitizing agent used for the management of acute decompensated heart failure. Levosimendan acts as a positive inotrope by sensitizing cardiac troponin C to calcium and exerts vasodilation by opening mitochondrial and sarcolemmal ATP-sensitive potassium channels. Levosimendan has been described to have beneficial effects in ventricular remodelling after myocardial infarction. The aims of the study were to characterize whether diabetic cardiomyopathy associates with cardiac dysfunction, cardiomyocyte apoptosis, hypertrophy and fibrosis in spontaneously diabetic Goto-Kakizaki (GK) rats, which were used to model type 2 diabetes. Protein expression and activation of the Akt FOXO3a and Sirt1 p53 pathways were examined in the development of ventricular remodelling in GK rats with and without myocardial infarction (MI). The third and fourth studies examined the effects of levosimendan on ventricular remodelling and gene expression in post-MI GK rats. The results demonstrated that diabetic GK rats develop both modest hypertension and features similar to diabetic cardiomyopathy including cardiac dysfunction, LV hypertrophy and fibrosis and increased apoptotic signalling. MI induced a sustained increase in cardiomyocyte apoptosis in GK rats together with aggravated LV hypertrophy and fibrosis. The GK rat myocardium exhibited decreased Akt- FOXO3a phosphorylation and increased nuclear translocation of FOXO3a and overproduction of the Sirt1 protein. Treatment with levosimendan decreased cardiomyocyte apoptosis, senescence and LV hypertrophy and altered the gene expression profile in GK rat myocardium. The findings indicate that impaired cardioprotection via Akt FOXO3a and p38 MAPK is associated with increased apoptosis, whereas Sirt1 functions in counteracting apoptosis and the development of LV hypertrophy in the GK rat myocardium. Overall, levosimendan treatment protects against post-MI ventricular remodelling and alters the gene expression profile in the GK rat myocardium.

Cox-2, tenascin, CRP, and ingraft chimerism in a model of post-transplant obliterative bronchiolitis

Chronic rejection in the form of obliterative bronchiolitis (OB) is the major cause of death 5 years after lung transplantation. The exact mechanism of OB remains unclear. This study focused on the role of cyclo-oxygenase (COX) -2, tenascin, and C-reactive protein (CRP) expression, and the occurrence of ingraft chimerism (= cells from two genetically distinct individuals in a same individual) in post-transplant OB development. In our porcine model, OB developed invariably in allografts, while autografts stayed patent. The histological changes were similar to those seen in human OB. In order to delay or prevent obliteration, animals were medicated according to certain protocol. In the beginning of the bronchial allograft reaction, COX-2 induction occurred in airway epithelial cells prior to luminal obliteration. COX-2 expression in macrophages and fibroblasts paralleled the onset of inflammation and fibroblast proliferation. This study demonstrated for the first time, that COX-2 expression is associated with the early stage of post- transplant obliterative airway disease. Tenascin expression in the respiratory epithelium appeared to be predictive of histologic features observed in human OB, and influx of immune cells. Expression in the bronchial wall and in the early obliterative lesions coincided with the onset of onset of fibroblast and inflammatory cell proliferation in the early stage of OB and was predictive of further influx of inflammatory and immune cells. CRP expression in the bronchial wall coincided with the remodelling process. High grade of bronchial wall CRP staining intensity predicted inflammation, accelerated fibroproliferation, and luminal obliteration, which are all features of OB. In the early obliterative plaque, majority of cells expressed CRP, but in mature, collagen-rich plaque, expression declined. Local CRP expression might be a response to inflammation and it might promote the development of OB. Early appearance of chimeric (= recipient-derived) cells in the graft airway epithelium predicted epithelial cell injury and obliteration of the bronchial lumen, which both are features of OB. Chimeric cells appeared in the airway epithelium after repair following transplantation-induced ischemic injury. Ingraft chimerism might be a mechanism to repair alloimmune-mediated tissue injury and to protect allografts from rejection after transplantation. The results of this study indicate, that COX-2, tenascin, CRP, and ingraft chimerism have a role in OB development. These findings increase the understanding of the mechanisms of OB, which may be beneficial in further development of diagnostic options.

Threshold voltage model for accumulation mode polycrystalline SOI MOSFETs and comparisons with experimental results

In this paper, a simple but accurate semi analytical charge sheet model is presented for threshold voltage of accumulation mode polycrystalline silicon on insulator (PSOI) MOSFETs. In this model, we define the threshold voltage (V-T) of the polysilicon accumulation mode MOSFET as the gate voltage required to raise the surface potential (phi(s)) to a value phi(sT) necessary to overcome the charge trapping in the grain boundary and to create channel accumulation charge that is equal to the channel accumulation charge available in the case of single crystal silicon accumulation mode MOSFET at that phi(sT). The correctness of the model is demonstrated by comparing the theoretically estimated values of threshold voltage with the experimentally measured threshold voltages on the accumulation mode PSOI MOSFETs fabricated in the laboratory using LPCVD polysilicon layers doped with boron to achieve dopant densities in the range 3.3 x 10(-15)-5 x 10(17)/cm(3). Further, it is shown that the threshold voltage values of accumulation mode PSOI MOSFETs predicted by the present model match very closely with the experimental results, better than those obtained with the models previously reported in the literature. (C) 2012 Elsevier B.V. All rights reserved.

Assessment of post-harvest losses in Nigeria fishery: the Kainji Lake model

The paper provides a description of a methodology used for quantitative assessment of post harvest losses in the Kainji Lake Fishery (Nigeria). The sample population was made up of 314 fisherfolk, 115 processors, 125 fish buyers and 111 fish sellers. For the determination of handling losses, 24,839 fishes weighing 2,389.31 kg belonging to 43 species were examined of which 10% by number and 9% by weight deteriorated at checking and 4% by number and 3% by weight at landing. Processing losses recorded 22% by number and 16% by weight deteriorated prior to and during smoking with the traditional 'Banda' kiln. During marketing, 16% of fish sold had deteriorated and 6% by weight of fish bought also deteriorated, mainly due to insect infestation during storage. Based on the 1995 yield estimate for Kainji Lake fishery, approximately 1000 tons of fish estimated at 80 million Naira were lost during handling alone. This figure would be much higher if the level of losses during processing and marketing are included. This assessment technique is recommended for use in obtaining quantifiable data on post harvest losses from other water bodies in Nigeria

Ethylene oxidation over platinum: In situ electrochemically controlled promotion using Na-beta'' alumina and studies with a Pt(111)/Na model catalyst

Electrochemically modified ethylene oxidation over a PI film supported on the Na+ ion conductor beta '' alumina has been studied over a range of conditions encompassing both promotion and poisoning, The system exhibits reversible behavior, and the data are interpreted in terms of (i) Na-enhanced oxygen chemisorption and (ii) poisoning of the surface by accumulation of Na compounds. At low Na coverages the first effect results in increased competitive adsorption of oxygen at the expense of ethylene, resulting in an increased rate, At very negative catalyst potentials (high Na coverage) both effects operate to poison the system: the increased strength of the Pt-O bond and coverage of the catalytic surface by compounds of Na strongly suppress the rate, Kinetic and spectroscopic results for ethylene oxidation over a Pt(111)-Na model catalyst shed light on important aspects of the electrochemically controlled system, Low levels of Na promote the reaction and high levels poison it, mirroring the behavior observed under electrochemical control and strongly suggesting that sodium pumped from the solid electrolyte is the key species, XP and Auger spectra show that under reaction conditions, the sodium exists as a surface carbonate. Post-reaction TPD spectra and the use of (CO)-C-13 demonstrate that CO is formed as a stable reaction intermediate, The observed activation energy (56 +/- 3 kJ/mol) is similar to that measured for CO oxidation under comparable conditions, suggesting that the rate limiting step is CO oxidation. (C) 1996 Academic Press, Inc.

Building Trust in a Post-Conflict Society: An Integrative Model of Intergroup Contact and Intergroup Emotions.

Across one longitudinal and two cross-sectional surveys in Northern Ireland, we tested a model of intergroup relations in which out-group attitudes and behavioral tendencies are predicted by cross-group friendship and positive intergroup appraisals, mediated by intergroup emotions and out-group trust. In study 1, out-group friendship at time 1 predicted out-group trust at time 2 (one year later), controlling for prior out-group trust. In study 2, positive and negative intergroup emotions mediated the effects of friendship on positive and negative behavioral tendencies and attitudes. In study 3, a confirmatory factor analysis indicated that trust and emotions are distinct constructs with unique predictive contributions. We then tested a model in which cross-group friendship predicted intergroup emotions and trust through intimate self-disclosure in out-group friendships. Our findings support an integration of an intergroup emotions framework with research highlighting the importance of cross-group friendship in fostering positive intergroup outcomes.

Functional analysis of String/CDC25 phosphatase in post-mitotic neurons

Cell cycle and differentiation are two highly coordinated processes during organ development. Recent studies have demonstrated that core cell cycle regulators also play cell cycle-independent functions in post-mitotic neurons, and are essential for the maintenance of neuronal homeostasis. CDC25 phosphatases are well-established CDK activators and their activity is mainly associated to proliferating tissues. The expression and activity of mammalian CDC25s has been reported in adult brains. However, their physiological relevance and the potential substrates in a non-proliferative context have never been addressed. string (stg) encodes the Drosophila CDC25 homolog. Previous studies from our group showed that stg is expressed in photoreceptors (PRs) and in lamina neurons, which are two differentiated cell types that compose the fly visual system. The aims of this work are to uncover the function of stg and to identify its potential neuronal substrates, using the Drosophila visual system as a model. To gain insight into the function of stg in a non-dividing context we used the GAL4/UAS system to promote downregulation of stg in PR-neurons, through the use of an RNAi transgene. The defects caused by stg loss-of-function were evaluated in the developing eye imaginal disc by immunofluorescence, and during adult stages by scanning electron microscopy. This genetic approach was combined with a specific proteomic method, two-dimensional difference gel electrophoresis (2D-DIGE), to identify the potential substrates in PR-cells. Our results showed that stg downregulation in PRs affects the well-patterned retina organization, inducing the loss of apical maintenance of PR-nuclei on the eye disc, and ommatidia disorganization. We also detected an abnormal accumulation of cytoskeletal proteins and a disruption of the axon structure. As a consequence, the projection of PR-axons into the lamina and medulla neuropils of the optic lobe was impaired. Upon stg downregulation, we also detected that PR-cells accumulate Cyclin B. Although the rough eye phenotype observed upon stg downregulation suggests neurodegeneration, we did not detect neuronal death during larval stages, suggesting that it likely occurs during pupal stages or during adulthood. By 2D-DIGE, we identified seven proteins which were differentially expressed upon stg downregulation, and are potential neuronal substrates of Stg. Altogether, our observations suggest that Stg phosphatase plays an essential role in the Drosophila visual system neurons, regulating several cell components and processes in order to ensure their homeostasis.

Test of Hockman and Oldham's job characteristics model in a post-secondary educational setting

One hundred and seventy-two subj ects participated in this quantitative, correlational survey which tested Hackman and Oldham's Job Characteristics Model in an educational setting. Subjects were Teaching Masters, Chairmen and Deans from an Ontario community college. The data were collected via mailed questionnaire, on all variables of the model. Several reliable, valid instruments were used to test the variables. Data analysis through Pearson correlation and stepwise multiple regression analyses revealed that core job characteristics predicted certain critical psychological states and that these critical psychological states, in turn were able to predict various personal and work outcomes but not absenteeism. The context variable, Satisfaction with Co-workers, was the only consistent moderating variable between core characteristics and critical psychological states; however, individual employee differences did moderate the relationship between critical psychological states and all of the personal and work outcomes except Internal Work Motivation. Two other moderator variables, Satisfaction with Context and Growth Need Strength, demonstrated an ability to predict the outcome General Job Satisfaction. The research suggests that this model may be used for job design and redesign purposes within the community college setting.