965 resultados para CENTRAL GLUCOCORTICOID-RECEPTORS


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Ornithine decarboxylase (ODC) regulates the synthesis of polyamines which are involved in many cellular functions e.g. proliferation and differentiation. Due to its critical role, ODC is a tightly regulated enzyme by antizymes and antizyme inhibitors. If the regulation fails, the activity of ODC increases and may lead to malignant transformation of a cell. Increased ODC activity is found in many common cancers, including colon, prostate, and breast cancer. In a transformed cell, dynamics of the actin cytoskeleton is disturbed. A small G-protein, RhoA regulates organization of the cytoskeleton, and its overactivity increases malignant potential of the cell. The present results indicate that covalent attachment of polyamines by transglutaminase is a physiological means of regulating the activity of RhoA. The translocation of RhoA to the plasma membrane, where it exerts its activity is dependent on the presence of catalytically active ODC. As the overactivity of ODC and RhoA are implicated in cell transformation, the results provide a mechanistic explanation of the interrelationship between the polyamine metabolism and the reorganization of the actin cytoskeleton occurring in cancer cells. ODC and polyamines have also an important role in the function of central nervous system. They participate in the regulation of brain morphogenesis in embryos. In adult nervous tissue, polyamines regulate K+ and glutamate channels. K+ inward rectifying channels control membrane potentials and NMDA-type glutamate receptors (NMDAR) regulate synaptic plasticity. High ODC activity and polyamine levels are considered important in the development of ischemic brain damage and they are implicated in the pathogenesis of Alzheimer s disease (AD). A homolog of ODC was cloned from a human brain cDNA library, and several alternatively spliced variants were detected in human brain and testis. The novel protein was nevertheless devoid of ODC catalytic activity. It was subsequently found to be a novel inductor of ODC activity and polyamine synthesis, called antizyme inhibitor 2 (AZIN2). The accumulation of AZIN2 in vesicle-like formations along the axons and beneath the plasma membrane of neurons as well as in steroid hormone producing Leydig cells and luteal cells of the gonads implies that AZIN2 plays a role in secretion and vesicle trafficking. An accumulation of AZIN2 was detected also in specimens of AD brains. This increased expression of AZIN2 was specific for AD and was not found in brains with other neurodegenerative diseases including CADASIL or dementia with Lewy bodies.

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This project employed a participatory development and extension (D&E) approach involving on-farm trials and capacity- building activities to improve the economic and environmental performance of grain and mixed farming enterprises in central Queensland (CQ). The project's activities delivered (1) enhanced knowledge and understanding of key system variables that underpin grain and mixed farming businesses, and parameter values for these variables in relation to a range of environmental and management factors, (2) new and refined practices, technologies and management strategies to sustain the profitability of cropping and (3) products and information to support continuous improvement in farm business performance.

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Increasing the productivity of irrigation water use and reducing energy use in rural irrigation within the Central Highlands and Dawson-Callide irrigation districts.

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Critical cellular decisions such as should the cell proliferate, migrate or differentiate, are regulated by stimulatory signals from the extracellular environment, like growth factors. These signals are transformed to cellular responses through their binding to specific receptors present at the surface of the recipient cell. The epidermal growth factor receptor (EGF-R/ErbB) pathway plays key roles in governing these signals to intracellular events and cell-to-cell communication. The EGF-R forms a signaling network that participates in the specification of cell fate and coordinates cell proliferation. Ligand binding triggers receptor dimerization leading to the recruitment of kinases and adaptor proteins. This step simultaneously initiates multiple signal transduction pathways, which result in activation of transcription factors and other target proteins, leading to cellular alterations. It is known that mutations of EGF-R or in the components of these pathways, such as Ras and Raf, are commonly involved in human cancer. The four best characterized signaling pathways induced by EGF-R are the mitogen-activated protein kinase cascades (MAPKs), the lipid kinase phosphatidylinositol 3 kinase (PI3K), a group of transcription factors called Signal Transducers and Activator of Transcription (STAT), and the phospholipase Cγ; (PLCγ) pathways. The activation of each cascade culminates in kinase translocation to the nucleus to stimulate various transcription factors including activator protein 1 (AP-1). AP-1 family proteins are basic leucine zipper (bZIP) transcription factors that are implicated in the regulation of a variety of cellular processes (proliferation and survival, growth, differentiation, apoptosis, cell migration, transformation). Therefore, the regulation of AP-1 activity is critical for the decision of cell fate and their deregulated expression is widely associated with many types of cancers, such as breast and prostate cancers. The aims of this study were to characterize the roles of EGF-R signaling during normal development and malignant growth in vitro and in vivo using different cell lines and tissue samples. We show here that EGF-R regulates cell proliferation but is also required for regulation of AP-1 target gene expression in fibroblasts in a MAP-kinase mediated manner. Furthermore, EGF-R signaling is essential for enterocyte proliferation and migration during intestinal maturation. EGF-R signaling network, especially PI3-K-Akt pathway mediated AP-1 activity is involved in cellular survival in response to ionizing radiation. Taken together, these results elucidate the connection of EGF-R and AP-1 in various cellular contexts and show their importance in the regulation of cellular behaviour presenting new treatment cues for intestinal perforations and cancer therapy.

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This project has delivered outcomes that address major agronomic and crop protection issues closely linked to the profitability and sustainability of cotton production enterprises in CQ. From an agronomic perspective, the CQ environment was always though to support economically viable cotton production in a wide sowing window from the middle of September to early January prior to this research. The ideal positioning of Bollgard II varieties in the CQ planting window was, therefore, critical to the future of the local cotton industry because growers needed baseline information to determine how best to take advantage of the higher yield potential offered by the Bt cotton technology, optimise irrigation water use and fibre characteristics. The project’s outputs include a number of key agronomic findings. Over three growing seasons, Bollgard II crop planted in the traditional sowing window from the middle of September to the end of October consistently produced the highest yields. The project delivers a clear and quantitative assessment of the impacts of planting outside the traditional cropping window - a yield penalty of between 1-4 bales/ha for November and December planted cotton. Whilst yield penalties associated with December-planted crops are clearly linked to declining heat units in the second half of the crop and a cool finish, those associated with November-planted cotton are not consistent with the theoretical yield potential for this sowing date. Further research to understand and minimize the physiological constraints on November-planted cotton would give CQ cotton growers far greater flexibility to develop mixed/double/rotation cropping farming systems that are relevant to the rapidly evolving nature of Agricultural production in Australia. The equivalence of cultivar types with clearly distinguishable, genetically based growth habits, demonstrated in this project, gives growers important information for making varietal choices. The entomological outcomes of this project represent strategic and tactical tools that are highly relevant to the viability and profitability of the cotton industry in Australia. The future of the cotton industry is inextricably linked to the survival and efficacy of GM cotton. Research done in the Callide irrigation area demonstrates the unquestionable potential for development of alternative and highly effective resistance management strategies for Bollgard II using novel technologies and strategies based on products such as Magnet®. Magnet® and similar technologies will be increasingly important in strategies to preserve the shelf life and efficacy of current and future generations of GM technology. However, more research will be required to address logistical and operational issues related to these new technologies before they can be fully exploited in commercial production systems. From an economic perspective, SLW is the sleeping giant in terms of insect nemeses of cotton, particularly from the standpoint of climate change and an increasingly warmer production environment. An effective sampling and management strategy for SLW which has been delivered by this project will go a long way towards minimising production costs in an environment characterised by rapidly rising input costs. SLW has the potential to permanently debilitate the national cotton industry by influencing market sentiment and quality perceptions. Field validation of the SLW population sampling models and management options in the Dawson irrigation area cotton and southern Queensland during 2006-07 documents the robustness of the entomological research outcomes achieved through this project.

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R&D to facilitate incorporation of grain and pulse crop phases in Central Queensland irrigated cotton monoculture systems and improve profitability of regional cropping systems.

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Sustainable Farming Systems for Central Queensland.

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Demonstrate potential benefits of various Precision Agricultural technologies to Central Queensland farming community.

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Developing best practices in Central Queensland to (a) manage difficult to control weeds; (b) improve herbicide efficacy under adverse conditions, and (c) manage weeds in wide-row crop systems.

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Improved economic and social performance of grain and mixed farming businesses in Central Queensland.

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Control measures for an unidentified disorder in sunflower crops in Central Queensland.