5 resultados para MEDIATED TRANSFORMATION
em Digital Commons at Florida International University
Resumo:
Breast cancer is a disease associated with excess exposures to estrogens. While the mode of cancer causation is unknown, others have shown that oxidative stress induced by prolonged exposure to estrogens mediates renal, liver, endometrial and mammary tumorigenesis though the mechanism(s) underling this process is unknown. In this study, we show that 4-hydroxyl 17β-estradiol (4-OHE2), a catechol metabolite of estrogen, induces mammary tumorigenesis in a redox dependent manner. We found that the mechanism of tumorigenesis involves redox activations of nuclear respiratory factor-1 (NRF1); a transcriptions factor associated with regulation of mitochondria biogenesis and oxidative phosphorylation (OXPHOS), as well as mediation of cell survival and growth of cells during periods of oxidative stress. Key findings from our study are as follows: (i) Prolonged treatments of normal mammary epithelial cells with 4-OHE2, increased the formation of intracellular reactive oxygen species (ROS). (ii) Estrogen-induced ROS activates redox sensitive transcription factors NRF1. (iii) 4-OHE2 through activation of serine-threonine kinase and histone acetyl transferase, phosphorylates and acetylate NRF1 respectively. (iv) Redox mediated epigenetic modifications of NRF1 facilitates mammary tumorigenesis and invasive phenotypes of breast cancer cells via modulations of genes involved in proliferation, growth and metastasis of exposed cells. (v) Animal engraftment of transformed clones formed invasive tumors. (vi) Treatment of cells or tumors with biological or chemical antioxidants, as well as silencing of NRF1 expressions, prevented 4-OHE2 induced mammary tumorigenesis and invasive phenotypes of MCF-10A cells. Based on these observations, we hypothesize that 4-OHE2 induced ROS epigenetically activate NRF1 through its phosphorylation and acylation. This, in turn, through NRF1-mediated transcriptional activation of the cell cycle genes, controls 4-OHE2 induced cell transformation and tumorigenesis.^
Resumo:
Iron oxides and arsenic are prevalent in the environment. With the increase interest in the use of iron oxide nanoparticles (IONPs) for contaminant remediation and the high toxicity of arsenic, it is crucial that we evaluate the interactions between IONPs and arsenic. The goal was to understand the environmental behavior of IONPs in regards to their particle size, aggregation and stability, and to determine how this behavior influences IONPs-arsenic interactions. ^ A variety of dispersion techniques were investigated to disperse bare commercial IONPs. Vortex was able to disperse commercial hematite nanoparticles into unstable dispersions with particles in the micrometer size range while probe ultrasonication dispersed the particles into stable dispersions of nanometer size ranges for a prolonged period of time. Using probe ultrasonication and vortex to prepare IONPs suspensions of different particle sizes, the adsorption of arsenite and arsenate to bare hematite nanoparticles and hematite aggregates were investigated. To understand the difference in the adsorptive behavior, adsorption kinetics and isotherm parameters were determined. Both arsenite and arsenate were capable of adsorbing to hematite nanoparticles and hematite aggregates but the rate and capacity of adsorption is dependent upon the hematite particle size, the stability of the dispersion and the type of sorbed arsenic species. Once arsenic was adsorbed onto the hematite surface, both iron and arsenic can undergo redox transformation both microbially and photochemically and these processes can be intertwined. Arsenic speciation studies in the presence of hematite particles were performed and the effect of light on the redox process was preliminary quantified. The redox behavior of arsenite and arsenate were different depending on the hematite particle size, the stability of the suspension and the presence of environmental factors such as microbes and light. The results from this study are important and have significant environmental implications as arsenic mobility and bioavailability can be affected by its adsorption to hematite particles and by its surface mediated redox transformation. Moreover, this study furthers our understanding on how the particle size influences the interactions between IONPs and arsenic thereby clarifying the role of IONPs in the biogeochemical cycling of arsenic.^
Resumo:
Recent studies found that organizations have been investing significant capital in developing teams and employees in geographic areas where labor and resources are considerably cheaper. Furthermore, organizations are moving core operational activities such as research and development and back-office processes to globally distributed teams. ^ However, several factors that are inherent to these virtual teams can have a negative impact on employee perceptions and engagement; specifically, the physical and temporal differences between employees and their supervisors, the lack of meaningful social interaction intrinsic to working relationships, and cultural biases that can be fostered when close, daily interactions is not there to help bridge the dissimilarity. ^ When strategies are not in place to mitigate these deficiencies, it can cause virtual employees to disengage emotionally and intellectually from the organization, or lead them to feel justified in working against the best interest of the company. ^ Past research indicates that although deviant behavior in the workplace is not new, transgressions committed by employees have been increasing significantly every year. Beyond the focus of why employees are motivated to act against the organization, to what extent do the recent changes to the organization’s structure influence this type of behavior through their actions at the macro (organizational) and micro level (leadership). ^ In addition, there is a related phenomenon that has aided the transformation of the workplace—namely, the ubiquity of technology. In the context of workplace deviance, established research has documented an increasing trend of employees utilizing company technology as a medium and amplifier when harming the organization. It is important to understand whether technology has facilitated or hindered workplace deviance by virtue of the technology itself (as a means), and as part of the new employee roles created by the evolving technology (i.e., virtual employees). Therefore, it is important to identify how individual attitudes and behaviors can be affected by an employee’s degree of virtuality. ^ This study will add to the understanding of how social interaction and physical proximity, leadership and other perception factors contribute to the changes organizations are experiencing as their structure evolves and adapts to compete in the new global environment. ^
Resumo:
Recent studies found that organizations have been investing significant capital in developing teams and employees in geographic areas where labor and resources are considerably cheaper. Furthermore, organizations are moving core operational activities such as research and development and back-office processes to globally distributed teams. However, several factors that are inherent to these virtual teams can have a negative impact on employee perceptions and engagement; specifically, the physical and temporal differences between employees and their supervisors, the lack of meaningful social interaction intrinsic to working relationships, and cultural biases that can be fostered when close, daily interactions is not there to help bridge the dissimilarity. When strategies are not in place to mitigate these deficiencies, it can cause virtual employees to disengage emotionally and intellectually from the organization, or lead them to feel justified in working against the best interest of the company. Past research indicates that although deviant behavior in the workplace is not new, transgressions committed by employees have been increasing significantly every year. Beyond the focus of why employees are motivated to act against the organization, to what extent do the recent changes to the organization’s structure influence this type of behavior through their actions at the macro (organizational) and micro level (leadership). In addition, there is a related phenomenon that has aided the transformation of the workplace – namely, the ubiquity of technology. In the context of workplace deviance, established research has documented an increasing trend of employees utilizing company technology as a medium and amplifier when harming the organization. It is important to understand whether technology has facilitated or hindered workplace deviance by virtue of the technology itself (as a means), and as part of the new employee roles created by the evolving technology (i.e, virtual employees). Therefore, it is important to identify how individual attitudes and behaviors can be affected by an employee’s degree of virtuality. This study will add to the understanding of how social interaction and physical proximity, leadership and other perception factors contribute to the changes organizations are experiencing as their structure evolves and adapts to compete in the new global environment.
Resumo:
Iron oxides and arsenic are prevalent in the environment. With the increase interest in the use of iron oxide nanoparticles (IONPs) for contaminant remediation and the high toxicity of arsenic, it is crucial that we evaluate the interactions between IONPs and arsenic. The goal was to understand the environmental behavior of IONPs in regards to their particle size, aggregation and stability, and to determine how this behavior influences IONPs-arsenic interactions. A variety of dispersion techniques were investigated to disperse bare commercial IONPs. Vortex was able to disperse commercial hematite nanoparticles into unstable dispersions with particles in the micrometer size range while probe ultrasonication dispersed the particles into stable dispersions of nanometer size ranges for a prolonged period of time. Using probe ultrasonication and vortex to prepare IONPs suspensions of different particle sizes, the adsorption of arsenite and arsenate to bare hematite nanoparticles and hematite aggregates were investigated. To understand the difference in the adsorptive behavior, adsorption kinetics and isotherm parameters were determined. Both arsenite and arsenate were capable of adsorbing to hematite nanoparticles and hematite aggregates but the rate and capacity of adsorption is dependent upon the hematite particle size, the stability of the dispersion and the type of sorbed arsenic species. Once arsenic was adsorbed onto the hematite surface, both iron and arsenic can undergo redox transformation both microbially and photochemically and these processes can be intertwined. Arsenic speciation studies in the presence of hematite particles were performed and the effect of light on the redox process was preliminary quantified. The redox behavior of arsenite and arsenate were different depending on the hematite particle size, the stability of the suspension and the presence of environmental factors such as microbes and light. The results from this study are important and have significant environmental implications as arsenic mobility and bioavailability can be affected by its adsorption to hematite particles and by its surface mediated redox transformation. Moreover, this study furthers our understanding on how the particle size influences the interactions between IONPs and arsenic thereby clarifying the role of IONPs in the biogeochemical cycling of arsenic.