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Caleb C. Roth Randolph D. Glickman Stacey L. Martens Ibtissam Echchgadda Hope T. Beier Ronald A. Barnes Bennett L. Ibey 《Biochemistry and Biophysics Reports》2017
BackgroundExposure of cells to very short (<1 µs) electric pulses in the megavolt/meter range have been shown to cause a multitude of effects, both physical and molecular in nature. Physically, nanosecond electrical pulses (nsEP) can cause disruption of the plasma membrane, cellular swelling, shrinking and blebbing. Molecularly, nsEP have been shown to activate signaling pathways, produce oxidative stress, stimulate hormone secretion and induce both apoptotic and necrotic death. We hypothesize that studying the genetic response of primary human dermal fibroblasts exposed to nsEP, will gain insight into the molecular mechanism(s) either activated directly by nsEP, or indirectly through electrophysiology interactions.MethodsMicroarray analysis in conjunction with quantitative real time polymerase chain reaction (qRT-PCR) was used to screen and validate genes selectively upregulated in response to nsEP exposure.ResultsExpression profiles of 486 genes were found to be significantly changed by nsEP exposure. 50% of the top 20 responding genes coded for proteins located in two distinct cellular locations, the plasma membrane and the nucleus. Further analysis of five of the top 20 upregulated genes indicated that the HDFa cells’ response to nsEP exposure included many elements of a mechanical stress response.ConclusionsWe found that several genes, some of which are mechanosensitive, were selectively upregulated due to nsEP exposure. This genetic response appears to be a primary response to the stimuli and not a secondary response to cellular swelling.General significanceThis work provides strong evidence that cells exposed to nsEP interpret the insult as a mechanical stress. 相似文献
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Samuel Hope 《Arts Education Policy Review》2013,114(4)
Abstract Jeremy Rifkin. Time Wars. New York: Touchstone Books, Simon & Schuster, 1989. 302 pp. $9.95 paperback. 相似文献
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David Hope Timothy Bates Lars Penke Alan J. Gow John M. Starr Ian J. Deary 《Economics & Human Biology》2013,11(2):236-244
The association of socioeconomic status (SES) with a range of lifecourse outcomes is robust, but the causes of these associations are not well understood. Research on the developmental origins of health and disease has led to the hypothesis that early developmental disturbance might permanently affect the lifecourse, accounting for some of the burden of chronic diseases such as coronary heart disease. Here we assessed developmental disturbance using bodily and facial symmetry and examined its association with socioeconomic status (SES) in childhood, and attained status at midlife. Symmetry was measured at ages 83 (facial symmetry) and 87 (bodily symmetry) in a sample of 292 individuals from the Lothian Birth Cohort 1921 (LBC1921). Structural equation models indicated that poorer SES during early development was significantly associated with lower facial symmetry (standardized path coefficient ?.25, p = .03). By contrast, midlife SES was not significantly associated with symmetry. The relationship was stronger in men (?.44, p = .03) than in women (?.12, p = .37), and the effect sizes were significantly different in magnitude (p = .004). These findings suggest that SES in early life (but not later in life) is associated with developmental disturbances. Facial symmetry appears to provide an effective record of early perturbations, whereas bodily symmetry seems relatively imperturbable. As bodily and facial symmetries were sensitive to different influences, they should not be treated as interchangeable. However, markers of childhood disturbance remain many decades later, suggesting that early development may account in part for associations between SES and health through the lifecourse. Future research should clarify which elements of the environment cause these perturbations. 相似文献
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