562 research outputs found

    ARMCX proteins regulate mitochondrial function in the Retinal Pigment Epithelium

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    Retinal Pigment Epithelium (RPE) functions, including energy absorption, photo-pigment recycling, and oxidative stress regulation, depend on a healthy mitochondrial network. Notably, RPE mitochondrial integrity declines during aging and even more so Age-related Macular Degeneration (AMD). Healthy mitochondria pervade the entirety of the cell as an organelle network undergoing constant dynamic renewal through fusion, fission and mitophagy. Armadillo repeat-containing genes located on the X chromosome (Armcx) form an Eutharian specific cluster of 6 genes which are implicated in mitochondrial motility in axons and, more generally, in mitophagy (as substrates of Parkin). Armcx6 is up-regulated in differentiated RPE whilst Armcx3 is down-regulated in AMD, collectively suggesting an important role in the homeostasis of RPE. This study specifically analysed the role of Armcx proteins in RPE cells. Armcx1, 2, 3 and 6 but not 4 or 5 are found as bona fide mitochondrial regulators and to be upregulated in RPE differentiation in vitro. Further analysis focused on Armcx1 and Armcx2 showed both proteins to affect mitochondrial network differently in RPE. Endogenous Armcx1 and Armcx2 were strongly associated with mitochondria in ARPE-19 cells and strongly expressed in the RPE layer of human retina. Armcx1 knockdown resulted in increased mitochondrial motility, whereas Armcx2 depletion led to decreased mitochondrial movements. Armcx overexpression resulted in aggregation and Page | 6 reduced mobility of mitochondria indicating disrupted dynamics. Armcx1 and Armcx2 knockdown resulted in fragmented mitochondria, however with different phenotypes, suggesting enhanced fission and/or mitophagy. Indeed, Armcx1 knockdown showed increased Parkin activation upon mitophagy induction, whereas Armcx2 resulted in no difference. In addition, Lamp2 expression was also affected differently, by Armcx1 depletion leading to upregulated Lamp2, in contrast to Armcx2 knockdown which decreased Lamp2 levels. Moreover, compensatory experiments using marsupial Armc10 revealed that Armcx1 and Armcx2 have acquired novel roles during their evolution in the Eutherian clade, probably to fulfil new functions essential to support the more complex Eutherian clade

    COLLABORATIVE EFFECTIVE MODELS BETWEEN PRESCHOOL INSTITUTIONS, CHILDREN AND PARENTS

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    Harmonious development of the child's personality requires unity, coherence of all activities and actions on the part of adults. The role of the family in creating such coherence is paramount, because it is the first institution for socialization, having a decisive influence on the development of the basic personality traits of the child, the formation of his moral and positive potential. It was in the family that he received the first lessons in morality, character formation, citizenship. The starting positions are set in the family. Therefore, the work of preschool institutions is extremely important, one of the main ones, namely to multiply the pedagogical knowledge among parents.Key words: collaboration, models, preschools, family, childre

    Análisis económico-financiero de Simecal S.L.

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    A través del siguiente trabajo se realizará un análisis económico- financiero de la empresa Simecal S.L. El objetivo es ver cuál es el estado de salud de la empresa, en un periodo de cinco años, además de analizar su rentabilidad económica y financiera, así como su riesgo financiero. Por último, se procederá a la obtención del valor de la empresa, de la forma más precisa posible. La finalidad de este análisis es permitir a la empresa ver en qué situación se encuentra en la actualidad y tomar, en caso de darse una situación desfavorable, la mejor decisión económico-financiera para poder seguir operando en el futuroThe following work is an economic-financial analysis of the company Simecal S.L. The objective is to see what the situation of the company is, in a period of five years, in addition to analysing its economic and financial profitability as well as its financial risk. Finally, the value of the company will be obtained as precisely as possible. The purpose of this analysis is to enable the company to see where it is at present and to take, in case of an unfavourable situation, the best economic-financial decision to be able to continue operating in the future.Departamento de Economía Financiera y ContabilidadGrado en Administración y Dirección de Empresa

    Numerical analysis of stress distribution in polycrystalline microstructure

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    The paper presents a numerical analysis of stress distribution in micromechanical models in order to simulate microstructural mechanisms of microcrack initiation and propagation in polycrystalline metals. The analysis is based on plane-strain finite element crystal elasticity models. The microstructure is generated using Voronoi tessellation, encompassing random crystallographic orientation and position of grains that have different shapes and sizes. Since the correlation between the physical mechanisms of deformation and the microstructure is essential for sound understanding of crack initiation and propagation, the paper considers development of microstructural models of behaviour of anisotropic linear-elastic and elastic-plastic polycrystalline metals. The results indicate that the key factor for good agreement with the data obtained from polycrystalline microstructure, is the correct and proper interpretation of material heterogeneity between grains. The attention should be placed on proper material characterization, crystallographic slip mechanism representation and orientation

    Numerical analysis of stress distribution in polycrystalline microstructure

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    The paper presents a numerical analysis of stress distribution in micromechanical models in order to simulate microstructural mechanisms of microcrack initiation and propagation in polycrystalline metals. The analysis is based on plane-strain finite element crystal elasticity models. The microstructure is generated using Voronoi tessellation, encompassing random crystallographic orientation and position of grains that have different shapes and sizes. Since the correlation between the physical mechanisms of deformation and the microstructure is essential for sound understanding of crack initiation and propagation, the paper considers development of microstructural models of behaviour of anisotropic linear-elastic and elastic-plastic polycrystalline metals. The results indicate that the key factor for good agreement with the data obtained from polycrystalline microstructure, is the correct and proper interpretation of material heterogeneity between grains. The attention should be placed on proper material characterization, crystallographic slip mechanism representation and orientation

    Effects of Rimonabant on learning and memory of rats with olfactory bulbectomy

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    Olfactory bulbectomy (OBX) is an experimental model of depression, which has recently been used as a model of Alzheimer's disease due to the development of neurodegenerative changes in the brain. The OBX model in rodents is accompanied by biochemical, morphological and structural changes in the brain, as well as by many behavioral changes. A common finding in the OBX model are memory deficits, which are present in both depressive disorders and neurodegenerative diseases. There is evidence that the memory-impairing effect of cannabinoids is associated with activation of the cannabinoid CB1 receptors in the brain. The aim of the present study was to investigate the effects of the CB1 antagonist Rimonabant (SR 141716A) administered intragastrically daily for 14 days on the memory processes of OBX rats, tested in a passive avoidance (PA) paradigm. Rimonabant was administered to OBX rats, divided into three experimental groups: before OBX; immediately after OBX (1-14 days); with the presence of a depressive-like state (14-28 days after OBX).  Rimonabant showed a tendency to improve the learning and memory of sham-operated controls, whereas no significant change in the behavioral responses was observed upon administration 14 days before OBX. However, Rimonabant, administered immediately after OBX completely prevented the development of memory deficit in a PA test, while its administration 14-28 days after OBX ameliorated the memory disturbances induced by bulbectomy.The results indicate that the CB1 antagonist Rimonabant may ameliorate the development of a memory deficit in OBX rats

    Finite element analysis of fracture resistance parameters for stationary semi-elliptical surface cracks in high strength steel

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    This study deals with numerical simulations based on elastic-plastic finite element method for nonlinear stress analyses on pre-cracked tensile specimens with high strength properties. The influence of crack geometry on fracture resistance properties is considered with numerical analysis on models with two different cracks. Results on fracture resistance parameters are obtained for both simulated tensile panels with different crack lengths and width, referred as short and long crack. The obtained numerical results for crack resistance behaviour of tensile specimens are compared with data results from existing experimental investigations on specimens with same shape and material properties. Also, comparison is made with results obtained from similar standard experimental procedure. It is shown, that a proper combination of numerical and experimental procedures can lead research to significantly accurate results when investigating the fracture response of materials

    Finite element analysis of fracture resistance parameters for stationary semi-elliptical surface cracks in high strength steel

    Get PDF
    This study deals with numerical simulations based on elastic-plastic finite element method for nonlinear stress analyses on pre-cracked tensile specimens with high strength properties. The influence of crack geometry on fracture resistance properties is considered with numerical analysis on models with two different cracks. Results on fracture resistance parameters are obtained for both simulated tensile panels with different crack lengths and width, referred as short and long crack. The obtained numerical results for crack resistance behaviour of tensile specimens are compared with data results from existing experimental investigations on specimens with same shape and material properties. Also, comparison is made with results obtained from similar standard experimental procedure. It is shown, that a proper combination of numerical and experimental procedures can lead research to significantly accurate results when investigating the fracture response of materials

    EFL COLLEGE STUDENTS’ SELF-ESTEEM AND ITS CORRELATION TO THEIR ATTITUDES TOWARDS INCLUSIVE EDUCATION

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    This study deals with an important personality trait which is self-esteem and how this trait can effect directly on students decisions and relationships. More precisely, the present study attempts to show the kind of the correlation between students’ self-esteem and their attitudes towards inclusive education. Two instruments are used in this study to collect data; self-esteem questionnaire that have developed by Rosenberg (1965) and the attitude scale by Moberg & Savolainen (2003). The participants are 140 college male and female students, their ages range between 20-25 years. They are all from the English department, college of education for human science, University of Diyala, Iraq. Results of the study demonstrate that there is no significant difference between male and female college students in self-esteem and in their attitudes towards inclusive education though male students seem more inclined than female students. Results also show that there is a significant correlation between students’ self-esteem and their attitudes towards inclusive education

    Galectins in the Pathogenesis of Common Retinal Disease

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    Diseases of the retina are major causes of visual impairment and blindness in developed countries and, due to an ageing population, their prevalence is continually rising. The lack of effective therapies and the limitations of those currently in use highlight the importance of continued research into the pathogenesis of these diseases. Vascular endothelial growth factor (VEGF) plays a major role in driving vascular dysfunction in retinal disease and has therefore become a key therapeutic target. Recent evidence also points to a potentially similarly important role of galectins, a family of β-galactoside-binding proteins. Indeed, they have been implicated in regulating fundamental processes, including vascular hyperpermeability, angiogenesis, neuroinflammation, and oxidative stress, all of which also play a prominent role in retinopathies. Here, we review direct evidence for pathological roles of galectins in retinal disease. In addition, we extrapolate potential roles of galectins in the retina from evidence in cancer, immune and neuro-biology. We conclude that there is value in increasing understanding of galectin function in retinal biology, in particular in the context of the retinal vasculature and microglia. With greater insight, recent clinical developments of galectin-targeting drugs could potentially also be of benefit to the clinical management of many blinding diseases
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