411 research outputs found

    Makings of imagination in alternative cultural spaces in Cairo

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    To speak of space as a concept, how it is produced, de/reconstructed, and imagined is a process that involves multiplicities of understanding about the makings that take place. My concern is in this research is exploring the dynamic relationships that take place between cultural spaces in Cairo, the subjectivities of their participants and the possibilities that might be offered through these relations for a different social imagination that could be manifested in the details of their everydayness. The main question of my thesis is; In which ways and conditions can some of the contemporary cultural spaces in Cairo situate their presence and serve as a liberating spaces that nurture imaginations capable of transfiguring the status quo whether intellectual, social or political. My research questions are anchored in four focal theoretical concepts: space, subjectivity, imagination and how these concepts are manifested in everydayness. I will not deal with them as separate, linear or static concepts but as dimensions that are constantly in dynamic change in relation to each other. I will not attempt a cause/effect analysis and I am not after a comparative or a descriptive analysis of the two cultural spaces I chose ( Nahda Association- Jesuit\u27s culture centre in Cairo, The Choir Project of Cairo). I believe this different and dynamic configuration of theorizing will enable different moods of thinking and greater capacity of exploration to acquire different kind of knowledge about the contemporary moment in Cairo\u27s cultural scene, which is rapidly changing and how they can possibly provide fertile conditions for a different social imagination to take place

    Plethysmography Phenotype QTL in Mice Before and After Allergen Sensitization and Challenge

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    Allergic asthma is common airway disease that is characterized in part by enhanced airway constriction in response to nonspecific stimuli. Genome-wide association studies have identified multiple loci associated with asthma risk in humans, but these studies have not accounted for gene–environment interactions, which are thought to be important factors in asthma. To identify quantitative trait loci (QTL) that regulate responses to a common human allergen, we applied a house dust mite mouse (HDM) model of allergic airway disease (AAD) to 146 incipient lines of the Collaborative Cross (CC) and the CC founder strains. We employed a longitudinal study design in which mice were phenotyped for response to the bronchoconstrictor methacholine both before and after HDM sensitization and challenge using whole body plethysmography (WBP). There was significant variation in methacholine responsiveness due to both strain and HDM treatment, as reflected by changes in the WBP parameter enhanced pause. We also found that distinct QTL regulate baseline [chromosome (Chr) 18] and post-HDM (Chr 19) methacholine responsiveness and that post-HDM airway responsiveness was correlated with other features of AAD. Finally, using invasive measurements of airway mechanics, we tested whether the Chr 19 QTL affects lung resistance per se using C57BL/6J mice and a consomic strain but found that QTL haplotype did not affect lung resistance. We conclude that aspects of baseline and allergen-induced methacholine responsiveness are associated with genetic variation, and that robust detection of airway resistance QTL in genetically diverse mice will be facilitated by direct measurement of airway mechanics

    Ten Years of the Collaborative Cross

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    The February 2012 issues of GENETICS and G3: Genes, Genomes, Genetics present a collection of articles reporting recent advances from the international Collaborative Cross (CC) project. The goal of the CC project is to develop a new resource that will enhance quantitative trait locus (QTL) and systems genetic analyses in mice. The CC consists of hundreds of independently bred, octo-parental recombinant inbred lines (Figure 1). The work reported in these issues represents progress toward completion of the CC, proof-of-principle experiments using incipient inbred CC mice, and new research areas and complementary resources facilitated by the CC project

    The Design, Synthesis, and Evaluation of (I) Arylpiperazines and (II) Pyrazolopyrimidinones as potential anti-diabetic agents

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    Diabetes is a worldwide condition that affects millions of people of all ages and backgrounds. It strikes the rich and the poor, old and young, healthy and sick. Diabetes is one of the largest global health emergencies of the 21st century, where some regions of the world have a much higher occurrence than others. Diabetes occurs when there are increased levels of glucose in the blood due to the lack of insulin, or the inability of the body’s cells to respond to insulin. Type 2 diabetes accounts for approximately 90% of all cases of diabetes worldwide and continues to rise across all world regions. The goal of our research was to investigate two families of heterocyclic compounds that have potential as anti-diabetic agents. We postulated that an anti-diabetic effect might be achieved through the inhibition of complex I of the electron transport chain, which would make oxidative phosphorylation less efficient, and therefore require increased glucose uptake from the blood in order to maintain ATP levels. This would consequently lower blood glucose levels and the inhibitor would thus have a hypoglycaemic effect. Building on findings of previous members of our own research group and collaborators, we developed two families of compounds and evaluated them for their anti-diabetic biological activity. The first family investigated was the arylpiperazine family, which consisted of analogues of the hit compound RTC1. Here, structural variations were performed at five sites on RTC1. The second family explored was the pyrazolopyrimidinone bicycle family, which consisted of analogues of the hit compound RTC53. In this case, structural variations were carried out at two principle sites on RTC53. Hydrophobic, steric, and electronic effects were all explored for both families through the systematic structural modifications. One of the aims of the project, in addition to access a large number of compounds, was to develop improved methods for the synthesis of both families. For the arylpiperazine family, a simpler and higher yielding procedure for their synthesis was achieved. This method no longer required anhydrous conditions or elaborate work-up procedures. For the pyrazolopyrimidinone bicycle family, method development focused on establishing a “one-pot” microwave-assisted synthesis of the pyrazolopyrimidinone bicycle. This avoided the need to isolate and purify intermediates, and reduced total reaction times down to just over 2 hours. Full characterisation of all compounds synthesised was carried out using techniques such as 1H and 13C NMR spectroscopy, including 2D-NMR experiments, X-ray crystal analysis, infrared spectroscopy, and high-resolution mass spectrometry. A structure activity relationship study was performed by testing compounds from both families in (i) a whole cell, functional, glucose uptake assay and (ii) a complex I inhibition assay. The glucose uptake assay measured the amount of tritiated (3H) deoxy-2-glucose taken up by C2C12 mouse muscle cells and quantified the fold change using a protein assay to determine the number of cells present. The complex I assay determined a compound’s ability to inhibit NADH dehydrogenase, complex I of the electron transport chain, by measuring the change in ubiquinone absorbance. Using both these assays, we were able to establish active compounds, which had the potential of developing into anti-diabetic agents, and obtained a better understanding of the influence of structure on this anti-diabetic biological effect

    The Stolen River: Possession and Race Representation in Grenville's Colonial Narrative

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    Grenville’s representations of race and power relations in The Secret River offer important insights into the strategies and performance of whiteness in Australian contemporary literature, particularly in relation to the idea of the ‘reconciliation’ between white Australia and Indigenous peoples. This article attempts to map a context for representations of race in The Secret River in order to contribute to critiques of literary texts as manifestations of cultural territories consistent with the places and times which produce them

    Hepatoprotective effect of taurine and coenzyme Q10 and their combination against acrylamide-induced oxidative stress in rats

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    Purpose: To clarify the protective effects of Taurine (TA) and Coenzyme Q10 (CoQ10) for mitigation of acrylamide- induced oxidative damage. .Method: Acrylamide (AA), TA and CoQ10 were administered orally to rats for 2 and 4 weeks. Sixty albino rats of either sex weighing 200 ± 5 were randomly divided into five groups; control group, AA group, AA+ TA group, AA+ CoQ10 group and AA+ TA+ CoQ10 Group ( 15, 500 and 200 mg/kg/day dose, respectively). Hepatoprotection was assessed. The level of hepatic marker enzymes including serum lactate dehydrogenase (LDH), aspartate transaminase (AST) and alanine transaminase (ALT) were evaluated. The proinflammatory cytokines including serum levels of tumor necrosis factor-α (TNF- α), interleukin- 1β (IL- 1β) and interleukin-6(IL-6) were assessed. The levels of reduced glutathione (GSH), malondialdehyde (MDA) and myeloperoxidase (MPO) in liver homogenate were also performed.Results: TA or CoQ10 significantly decreased (p < 0.05) the elevation of hepatic markers (LDH, AST and ALT) induced by AA in rats. Reduction of serum proinflammatory cytokines (TNF-α, IL- 1β and IL-6) were also observed compared to AA group, and it was a time-effect relationship. Treatment with TA or CoQ10 also significantly reduced the oxidative stress induced by AA as shown by an increase in GSH level, and reduction of MDA level and MPO activities compared to rats treated with AA alone (p < 0.05). The hepatoprotective effect of both TA and CoQ10 combination was more efficient than the effect of either of them alone.Conclusion: The combination of TA and Co Q10 possesses a good potential to inhibit oxidative stress from liver and also exhibits anti-inflammatory activity. Thus, they have the potential to be used to mitigate AA- induced liver injury.Keywords: Taurine, Coenzyme Q10, Acrylamide, Oxidative stress, Biochemical profile, Proinflammatory cytokine

    Meta-analysis of airway epithelium gene expression in asthma

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    Differential gene expression in the airway epithelium of patients with asthma versus controls has been reported in several studies. However, there is no consensus on which genes are reproducibly affected in asthma. We sought to identify a consensus list of differentially expressed genes (DEGs) using a meta-analysis approach. We identified eight studies with data that met defined inclusion criteria. These studies comprised 355 cases and 193 controls and involved sampling either bronchial or nasal epithelium. We conducted study-level analyses, followed by a meta-analysis. Likewise, we applied a meta-analysis framework to the results of study-level pathway enrichment. We identified 1273 DEGs, 431 of which had not been identified in previous studies. 450 DEGs exhibited large effect sizes and were robust to study population differences in age, sex, race/ethnicity, medication use, smoking status and exacerbations. The magnitude of differential expression of these 450 genes was highly similar in bronchial and nasal airway epithelia. Meta-analysis of pathway enrichment revealed a number of consistently dysregulated biological pathways, including putative transcriptional and post-transcriptional regulators. In total, we identified a set of genes that is consistently dysregulated in asthma, that links to known and novel biological pathways, and that will inform asthma subtype identification

    Innovations and revolutions in reducing retinal ganglion cell loss in glaucoma

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    Introduction: Glaucoma remains the leading cause of irreversible blindness. Although the loss of retinal ganglion cells (RGCs) is an established hallmark of glaucoma, reduction of intraocular pressure (IOP) is a widely used evidence-based management approach, even in normotensive patients. However, despite optimal pressure control, some patients progress to lose vision. / Areas covered: This review provides a summary of the latest methods aimed at reducing RGC loss with the objective of preserving vision, categorized by the mechanism of action. We discuss both the newest ways in which IOP can be reduced, alongside ‘pressure-independent’ pharmacological therapies and developments in bioengineering. The conducted PubMed search included the terms: ‘glaucoma pathophysiology,’ ‘IOP-lowering agents,’ ‘retinal ganglion cell apoptosis,’ ‘neuroprotection,’ ‘stem cells,’ ‘imaging.’ / Expert opinion: With many agents failing to successfully translate into clinical use, further understanding of the underlying disease process is required, along with novel biomarkers that will enable timely and reliable quantification of treatment effect
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