196,363 research outputs found
Oxidative stress and hypoxia/reoxygenation trigger CD95 (APO-1/Fas) ligand expression in microglial cells
No full textApoptosis plays an important role in neurodegeneration, although the mechanisms and mediators in the brain are largely unknown. Because microglial cells have been suggested to contribute to apoptosis in neurological disorders, we investigated the expression of the death ligand CD95L in this cell type. We found that, compared to classical mediators of microglial activation, the most potent inducer of CD95L was oxidative stress. Exposure of microglial cells to H2O2 or paraquat rapidly triggered CD95L mRNA and protein expression, associated with the activation of transcription factor NF-kappaB. Enhanced expression of CD95L was further found following exposure of cells to hypoxia and subsequent reoxygenation. Our results indicate a potential role of CD95L in oxidative stress-mediated cell death, ischemia/reperfusion and other diseases with a disturbed redox balance
Extracellular ATP activates transcription factor NF-κB through the P2Z purinoreceptor by selectively targeting NF-κB p65 (RelA)
No full textCells of the macrophage lineage express a peculiar surface receptor for extracellular ATP, designated P2Z/P2X7 purinergic receptor, that induces pore formation and collapse of the plasma membrane potential. Although the function of the P2Z receptor is largely unknown, accumulating evidence implicates its role in cell signaling and immune reactions. Here, we investigated the effect of P2Z receptor ligation on the activation of NF-kappaB, a transcription factor controlling cytokine expression and apoptosis. Exposure of microglial cells to ATP but not other nucleotides resulted in potent NF-kappaB activation. This effect was specifically mediated by the P2Z receptor, because selective receptor antagonists prevented NF-kappaB activation. NF-kappaB activation required reactive oxygen intermediates and proteases of the caspase family, because it was abolished by antioxidants and specific protease inhibitors. The subunit composition of the ATP-induced NF- kappaB-DNA complex was rather unusual. Whereas exposure to LPS-induced prototypical NF-kappaB p50 homo- and p65 (RelA)/p50 heterodimers, ATP stimulation resulted in the sole appearance of a p65 homodimer. This is the first demonstration that a certain stimulus activates a particular NF-kappaB subunit. Because different NF-kappaB complexes exhibit distinct transcriptional and DNA-binding activities, ATP may control the expression of a subset of NF-kappaB target genes distinct from those activated by classical proinflammatory mediators
Dr. Duane M. Jackson, Morehouse College, July 2011
No full textThis video is a conversation with Dr. Duane M. Jackson. Dr. Jackson talks about his paper, "Recall and the Serial Position Effect: The Role of Primacy and Recency on Accounting Students' Performance." Jackie Daniel, AUC Woodruff Library, is the interviewer
"Reflections on the subject of Emigration from Europe with a view to Settlement in the United States" By M. Carey.
No full text"Reflections on the subject of Emigration from Europe with a view to Settlement in the United States: containing bried sketches of the moral and political character of those states.
By M. Carey, member of the American philosophical, and of the American Antiquarian Society, and author of The Olive Branch, Cindiciae Hibernicae, essays on banking, on political economy, and on internal improvement.
To which are now added the English editor's comments on the subject; together with Important Advice to Emigrants, and Cautions Against Impositions Practiced in the Outports
Dispelling the Myths Behind First-author Citation Counts
No full textWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
Dr. Glendon Swarthout
No full textHosted by Roger M. Busfield, MSU Assistant Professor of Speech and Theater, Meet the Author is designed to introduce a general audience to a contemporary author and their work through in-depth interviews. This episode features a conversation between Dr. Glendon Swarthout, prolific author and English professor at MSU, and assistant professors Sam S. Baskett and Theodore B. Strandness
Purinoceptor-mediated activation of transcription factors NFAT and NF-kB in microglial cells.
No full textNFAT and NF-kB are important transcriptional regulators that play a role in controlling the expression of several cytokines, cytokine receptors and adhesion molecules. The effect of extracellular ATP on the activation of NF-kB and NFAT was investigated in the mouse microglial cell lines N9 and N13. ATP potently activated NF-kB and NFAT with strikingly distinct kinetics. NFAT was induced as soon as 1 min after stimulation with the nucleotide, while NF-kB activation was quite delayed (3 h). Both NFAT-1 and NFAT-2 were activated by a calcineurin-dependent pathway that required influx of extracellular Ca2+. Inhibition of calcineurin and Ca2+ chelation prevented ATP-induced NFAT activation and nuclear translocation. Exposure to LPS induced the prototypical NF-kB p50 homo and p65/p50 heterodimers while ATP, only induced the peculiar p65 homodimer. NFAT and NF-kB activation involved a P2X-mediated pathway as oxidized ATP completely inhibited the activation of both factors and BzATP was a better agonist than ATP in inducing NFAT and NF-kB. Cells selected for the absence of P2X7 receptor but still expressing the P2Y subtype were refractory to ATP, suggesting that ATP-stimulated activation was a P2X7-mediated process. Furthermore, NF-kB activation required ROI production and involved proteasome activity, while secretion of soluble proteins was not required. Caspase-1 (ICE) was also activated during exposure to ATP
P2Z purinoreceptor ligation induces activation of caspases with distinct roles in apoptotic and necrotic alterations of cell death
No full textMyeloic cells express a peculiar surface receptor for extracellular ATP, called the P2Z/P2X7 purinoreceptor, which is involved in cell death signalling. Here, we investigated the role of caspases, a family of proteases implicated in apoptosis and the cytokine secretion. We observed that extracellular ATP induced the activation of multiple caspases including caspase-1, -3 and -8, and subsequent cleavage of the caspase substrates PARP and lamin B. Using caspase inhibitors, it was found that caspases were specifically involved in ATP-induced apoptotic damage such as chromatin condensation and DNA fragmentation. In contrast, inhibition of caspases only marginally affected necrotic alterations and cell death proceeded normally whether or not nuclear damage was blocked. Our results therefore suggest that the activation of caspases by the P2Z receptor is required for apoptotic but not necrotic alterations of ATP-induced cell death
Differential regulation and ATP requirement for caspase-8 and caspase-3 activation during CD95- and anticancer drug-induced apoptosis
No full textApoptosis is induced by different stimuli, among them triggering of the death receptor CD95, staurosporine, and chemotherapeutic drugs. In all cases, apoptosis is mediated by caspases, although it is unclear how these diverse apoptotic stimuli cause protease activation. Two regulatory pathways have been recently identified, but it remains unknown whether they are functionally independent or linked to each other. One is mediated by recruitment of the proximal regulator caspase-8 to the death receptor complex. The other pathway is controlled by the release of cytochrome c from mitochondria and the subsequent ATP-dependent activation of the death regulator apoptotic protease-activating factor 1 (Apaf-1). Here, we report that both pathways can be dissected by depletion of intracellular ATP. Prevention of ATP production completely inhibited caspase activation and apoptosis in response to chemotherapeutic drugs and staurosporine. Interestingly, caspase-8, whose function appeared to be restricted to death receptors, was also activated by these drugs under normal conditions, but not after ATP depletion. In contrast, inhibition of ATP production did not affect caspase activation after triggering of CD95. These results suggest that chemotherapeutic drug-induced caspase activation is entirely controlled by a receptor-independent mitochondrial pathway, whereas CD95-induced apoptosis can be regulated by a separate pathway not requiring Apaf-1 function
Simulation of thermal plant optimization and hydraulic aspects of thermal distribution loops for large campuses
No full textFollowing an introduction, the author describes Texas A&M University and its utilities system. After that, the author presents how to construct simulation models for chilled water and heating hot water distribution systems. The simulation model was used in a $2.3 million Ross Street chilled water pipe replacement project at Texas A&M University. A second project conducted at the University of Texas at San Antonio was used as an example to demonstrate how to identify and design an optimal distribution system by using a simulation model. The author found that the minor losses of these closed loop thermal distribution systems are significantly higher than potable water distribution systems. In the second part of the report, the author presents the latest development of software called the Plant Optimization Program, which can simulate cogeneration plant operation, estimate its operation cost and provide optimized operation suggestions. The author also developed detailed simulation models for a gas turbine and heat recovery steam generator and identified significant potential savings. Finally, the author also used a steam turbine as an example to present a multi-regression method on constructing simulation models by using basic statistics and optimization algorithms. This report presents a survey of the author??s working experience at the Energy Systems Laboratory (ESL) at Texas A&M University during the period of January 2002 through March 2004. The purpose of the above work was to allow the author to become familiar with the practice of engineering. The result is that the author knows how to complete a project from start to finish and understands how both technical and nontechnical aspects of a project need to be considered in order to ensure a quality deliverable and bring a project to successful completion. This report concludes that the objectives of the internship were successfully accomplished and that the requirements for the degree of Degree of Engineering have been satisfied
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