90 research outputs found
Neuroimmune modulation following traumatic stress in rats: evidence for an immunoregulatory cascade mediated by c-Src, miRNA222 and PAK1
No full textAbstract Background Neuroimmune modulation following traumatic stress is accompanied by cortical upregulation of c-Src expression, but the mechanistic details of the potential regulatory link between c-Src expression and immunosuppression have not been established. Methods We used a combination of techniques to measure temporal changes in: (i) the parallel expression of c-Src and microRNA222; (ii) levels of PAK1 (p21-activated kinase 1); and (iii) the association between PAK1 and interleukin 1β signaling, both in cortex of rats following traumatic stress and in primary cortical neurons. Techniques included real-time PCR, immunoprecipitation, western blotting and subcellular fractionation by discontinuous centrifugation. We also measured lymphocyte proliferation and natural killer (NK) cell activity. Results We confirm robust upregulation of c-Src expression following traumatic stress. c-Src upregulation was accompanied by marked increases in levels of miRNA222; other studied miRNAs were not affected by stress. We also established that PAK1 is a primary target for miRNA222, and that increased levels of miRNA222 following traumatic stress are accompanied by downregulation of PAK1 expression. PAK1 was shown to mediate the association of IL-1RI with lipid rafts and thereby enhance IL-1 signaling. Detailed analyses in cultured neurons and glial cells revealed that PAK1-mediated enhancement of IL-1RI activation is governed to a large extent by c-Src/miRNA222 signaling; this signaling played a central role in the modulation of lymphocyte proliferation and NK cell activity. Conclusions Our results suggest that neuroimmune modulation following traumatic stress is mediated by a cascade that involves c-Src-mediated enhancement of miRNA222 expression and downregulation of PAK1, which in turn impairs signaling via IL-1β/IL1-RI, leading to immunosuppression. The regulatory networks involving c-Src/miRNA222 and PAK1/IL-1RI signaling have significant potential for the development of therapeutic approaches designed to promote recovery following traumatic injury.</p
Age-Dependent Neuroimmune Modulation of IGF-1R in the Traumatic Mice
No full textAbstract Background Age-dependent neuroimmune modulation following traumatic stress is accompanied by discordant upregulation of Fyn signaling in the frontal cortex, but the mechanistic details of the potential cellular behavior regarding IGF-1R/Fyn have not been established. Methods Trans-synaptic IGF-1R signaling during the traumatic stress was comparably examined in wild type, Fyn (−/−) and MOR (−/−) mice. Techniques included primary neuron culture, in vitro kinase activity, immunoprecipitation, Western Blot, sucrose discontinuous centrifugation. Besides that, [3 H] incorporation was used to assay lymphocyte proliferation and NK cell activity. Results We demonstrate robust upregulation of synaptic Fyn activity following traumatic stress, with higher amplitude in 2-month mice than that in 1-year counterpart. We also established that the increased Fyn signaling is accompanied by its molecular connection with IGF-1R within the synaptic zone. Detained analysis using Fyn (−/−) and MOR (−/−) mice reveal that IGF-1R/Fyn signaling is governed to a large extent by mu opioid receptor (MOR), and with age-dependent manner; these signaling cascades played a central role in the modulation of lymphocyte proliferation and NK cell activity. Conclusions Our data argued for a pivotal role of synaptic IGF-1R/Fyn signaling controlled by MOR downstream signaling cascades were crucial for the age-dependent neuroimmune modulation following traumatic stress. The result here might present a new quality of synaptic cellular communication governing the stress like events and have significant potential for the development of therapeutic approaches designed to minimize the heightened vulnerability during aging.</p
The Economic Consequences of IPO Spinning
No full textUsing a sample of fifty-six companies going public in 1996--2000 in which top executives received allocations of other hot initial public offerings (IPOs) from the bookrunner, a practice known as spinning, we examine the consequences of spinning. The fifty-six IPOs had first-day returns that were, on average, 23% higher than similar IPOs. The profits collected by these executives were only a small fraction of the incremental amount of money left on the table by their companies when they went public. These companies were dramatically less likely to switch investment bankers in a follow-on offer: only 6% of issuers whose executives were spun switched underwriters, whereas 31% of other issuers switched. These findings suggest that the spinning of executives accomplished its goal of affecting corporate decisions. The Author 2010. Published by Oxford University Press on behalf of The Society for Financial Studies. All rights reserved. For Permissions, please e-mail: [email protected]., Oxford University Press.
Computational analysis of three-dimensional flow and mass transfer in a non-standard configuration for growth of a KDP crystal
No full text3D numerical simulation for single crystal growth of potassium dihydrogen phosphate in a new solution growth system
No full textRound and pleated blisters: interface delamination in thin film deposition
No full textElectron beam deposition is widely used in microelectronics manufacturing due to its ability to fabricate high-purity thin films at elevated rates. However, the formation of blisters during this process – resulting from delamination between the film and substrate – can compromise film integrity and adversely affect device performance. This study investigates the mechanisms behind blister formation during the deposition of gold/titanium (Au/Ti) films on SiO2/Si substrates with a polymethyl methacrylate (PMMA) layer, a common configuration in electronics. Two distinct types of blisters are identified: round blisters and pleated blisters. Elemental analysis and in situ heating experiments revealed that round blisters originate from delamination at the Au-Ti-PMMA/SiO₂ interface, while pleated blisters result from delamination between the Au-Ti film and the PMMA layer. We provide a mechanics model that can quantify the energy required to delaminate the film-substrate interface and the strain within the blister regions. The results offer valuable perspectives on both the fabrication of thin films and the potential application of strain engineering, where controlled blistering may enhance the functional performance of thin films for use in advanced microelectronics
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