Insights into the Possible Mechanisms By Which Platelet-Activating Factor and PAF-receptors Function in Vascular Smooth Muscle in Magnesium Deficiency and Vascular Remodeling: Possible Links to Atherogenesis, Hypertension and Cardiac Failure

Platelet-activating factor (PAF) is a phospholipid mediator and cell signaling molecule which displays multiple biological and pathophysiological attributes, running the gamut from inflammation to cell differentiation and proliferation [1-4]. As is well-known, PAF interacts with specific membrane PAF-receptors (PAF-Rs) to initiate all cellular responses via specific G-proteincoupled receptors [1-4]. Although these initiated membrane receptor phenomena are mostly established for several tissuecell systems [1-8], exactly how PAF and PAF-Rs cause vascular remodeling in hypertension and atherosclerosis is not clear. A little more than 15 years ago, PAF was identified as a molecule that stimulated activation of nuclear factor-kappaB (NF-kB

Killing the golden goose: balancing preservation and development in Wilmington, North Carolina

There is a delicate balance between preserving objects of the past and preparing for the future. While preservationists fight a noble battle in protecting artifacts and architecture which may possess historic significance, their endeavors impede the efforts of developers in reshaping the landscape. The story of downtown Wilmington’s revitalization process is a story of a city’s changing needs, and how one organization in particular, Downtown Area Revitalization Effort, Inc., worked to remedy the city’s ills. Established in response to urban sprawl and the impending construction of an indoor shopping mall, DARE initially used preservation as a tool for economic development, but with the passage of time and changes in administration, rehabilitation was replaced by marketing and development policies. However, such occurrences were not isolated to Wilmington. The pressure to cast aside preservation in favor of renewed expansion registered in downtown areas across the country. Though organizations in cities like Charleston and Savannah were successful in preserving their historic fabric through the practice of urban husbandry, other cities such as Chattanooga and Mobile eventually succumbed to increased development through long-term project planning. By examining the economic history of downtown Wilmington in relation to urban sprawl, this thesis argues that changes in the city’s political climate brought about a shift in DARE’s policies, as the organization moved from practical preservation to industrial recruiting and development

Investigation of endothelial cell injury and dysfunction induced by air pollutant benzo-a-pyrene-1,6-quinone: implications in chemical atherogenesis

Cardiovascular diseases (CVD) are the leading cause of death for men and women in the USA, and growing evidence has led to an increase in concern about the detrimental effect of airborne particulate matter (PM) on health and its relation to the development of CVD. Indeed, epidemiological studies have shown that there is a well-established association between PM and increased atherosclerosis morbidity and mortality. However, how PM induces atherosclerosis remains to be elucidated. PM is a heterogeneous mixture of incomplete combustion of organic matter and fossil fuels, which is made up of metals, aldehydes, polycyclic aromatic hydrocarbons (PAHs) including benzo-a-pyrene (BP), and a variety of quinones. BP is produced during incomplete combustion of organic matter such as coal, oil, garbage or other organic substances. BP-1,6-quinone (BP-1,6-Q) is derived from BP and is one of the important constituents of PM. It is generated through atmospheric transformations of BP by UV light or by the oxidation of BP via CYP450 enzymes within the cells. While endothelium has been suggested to be one of the well-known targets by air pollutants, the action of BP-1,6-Q in endothelial cells remains to be examined. We hypothesized that BP-1,6-Q could promote atherosclerosis through endothelial cell injury. The goal of this research project is to elucidate the effects and the underlying mechanism of BP-1,6-Q on endothelial injury using human EA.hy926 endothelial cells as a model system. The specific objectives of this study were; (1) to examine redox activity of BP-1,6-Q and the underlying molecular mechanisms involved, (2) to elucidate the role of cellular glutathione (GSH) in BP-1,6-Q- mediated cytotoxicity and cellular macromolecule damages, (3) to study the role of Phase II enzyme NADPH-quinone oxidoreductase-1 (NQO1) in BP-1,6-Q-mediated cytotoxicity and ROS production in human EA.hy926 endothelial cells. We first examined whether BP-1,6-Q at non-toxic concentrations (0.01-1 [lowercase Greek letter mu]M) could produce ROS in EA.hy926 endothelial cells as ROS is a key mediator of signaling pathways causing oxidative stress in the development of atherosclerosis. Using lucigenin- and luminol-derived chemiluminescence and 2’7’-Dichlorofluorescein diacetate (DCF-DA) flow cytometry assays, we have shown that BP-1,6-Q stimulated the production of reactive oxygen species (ROS) in a concentration-dependent manner. Furthermore, BP-1,6-Q-induced ROS was inhibited by rotenone (Rot) and antimycin A (AA), denoting the involvement of mitochondrial electron transport chain (METC) in redox cycling of BP-derived quinones in ROS overproduction. We have further demonstrated that BP-1,6-Q triggered endothelial-monocyte interaction and stimulated expression of vascular adhesion molecule-1 (VCAM-1). These results suggest that ROS production may partially mediate the inflammatory effect of BP-1,6-Q on endothelial inflammation. To further determine the mechanisms by which BP-1,6-Q produces ROS, we have determined the involvement of Phase II enzyme NQO1 in redox cycling of BP-1,6-Q. We have observed that inhibition of NQO1 showed a decrease in generation of BP-1,6-Q-mediated ROS, and augmentation of NQO1 resulted in a significant increase in BP-1,6-Q-induced ROS. Thus, our results reported for the first time that NQO1 plays a vital role in catalyzing redox activation of BP-1,6-Q to generate ROS in endothelial cells. In contrast, at higher concentrations (20-60 [lowercase Greek letter mu]M) BP-1,6-Q causes a significant decrease in cell viability and an increase in the necrotic type of cell death as measured by lactate dehydrogenase assay (LDH) and flow cytometric assays. We have also demonstrated that BP-1,6-Q imparts its toxicity by depleting cellular glutathione (GSH) and NQO1 resulting in cellular macromolecular damage in a concentration-dependent manner. Augmentation of cellular GSH and NQO1 showed significant protection against BP-1,6-Q-induced cell death. These results indicate that GSH and NQO1 might be first in the line of defense against BP-1,6-Q induced cytotoxicity. Interesting, our results further showed that NQO1-mediated ROS production by BP-1,6-Q is not associated with BP-1,6-Q induced cell injury suggesting that BP-1,6-Q can be toxic to endothelial cells by itself without any biotransformation to toxic metabolites. Taken together, this thesis study conducted using human EA.hy926 endothelial cells as a model system expanded our understanding of the possible involvement of mitochondria and cellular GSH and NQO1 in BP-1,6-Q mediated cytotoxicity as well its ROS production. These studies will contribute to our ability to assess the cardiovascular risk of human exposure to air pollutant to BP-1,6-Q.[This abstract has been edited to remove characters that will not display in this system. Please see the PDF for the full abstract.]]]> 2018 Endothelial cells Polycyclic aromatic hydrocarbons $x Physiological effect Air$x Pollution Cardiovascular system $x Diseases Atherosclerosis English http://libres.uncg.edu/ir/uncg/f/Shah_uncg_0154D_12524.pdf oai:libres.uncg.edu/23475 2018-09-07T13:18:05Z UNCG Assessment of entomological risk for Lyme borreliosis along a north-to-south gradient from southern Virginia into North Carolina NC DOCKS at The University of North Carolina at Greensboro Teague, Jimmie Lee <![CDATA[Lyme disease (LD) has become the most prevalent vector-borne disease in the United States and the sixth Nationally Notifiable disease. Surveillance of Lyme disease from the 1992-2016 has shown a sustained documented expansion of LD moving south into the border of Virginia and North Carolina, west into West Virginia, Tennessee, northwest into North Dakota, and North into Canada. This expansion of LD seems to be associated with expansion of the disease vector Ixodes scapularis, with newly established populations in the southwestern Appalachian and Piedmont regions of Virginia. The goal of the study was to characterize the entomological risk of the spread of LD from VA into NC. To determine the distribution and infection prevalence of I. scapularis along a northeastern-to-southwestern gradient from VA to NC, tick-flagging and hunter-harvested deer tick collecting approaches were used with samples tested by the CDC for infection. Flagging was comprised of periodic sampling sessions from October 2015 to July 2017, conducted at Fairy Stone, Mayo River, Hanging Rock, Pilot Mountain, Yadkin Island Park, and Lake Norman State Parks. Hunted deer processing stations Hilltop Farms (Walnut Cove, NC) and Game Butchers (Troutman, NC), were used for collecting ticks from hunter-harvested deer covering counties for the northern, central and southern North Carolina Piedmont regions. Ticks collected by flagging were suggestive of a north-to-south trend with no significant difference among the northernmost State Parks and a significant difference in abundance between the northern and southernmost State Parks. The highest number of I. scapularis ticks (0.7 per 100m) was collected from the north-most Virginia’s Fairy Stone and Hanging Rock State Parks, but no I. scapularis were collected from the southernmost Lake Norman location. Infection prevalence of ticks collected by flagging exhibited a general north-to-south declining trend. Though not statistically significant with highest infection rate approximately 25% at the north-most Fairy Stone State Park. For deer collected ticks, there was a significant north-to-south decrease in tick burden per deer, with the northern region located on the VA-NC border having the highest number of I. scapularis (6.0 per deer), followed by the central and the southern regions of NC. Infection prevalence of sampled ticks from deer are suggestive of a declining trend although not significant, with the northern region having the highest (17%), followed by the central region (11%), and no infection present in the southern region. Ixodes scapularis results collected from flagging, and hunter-harvested deer are highly suggestive of a north-to-south gradient in I. scapularis densities with Alexander and Iredell being the south-most I. scapularis positive counties. Borrelia burgdorferi infection results also suggest a north-to-south distribution, with B. burgdorferi appearing to have only made it as far south as the central counties of Yadkin and Forsyth. Entomological risk estimates for density of infected nymphs (DIN) and adults (DIA) of flagging and hunted deer also showed a north-to-south trend with Fairy Stone State Park having the highest (0.033) DIN and northern NC region having the highest (0.808) DIA. The results are consistent with first the spread of the vector followed by the pathogen

A comparative study of Brenda Ueland's autobiography <i>ME (Brenda Ueland)</i> to the song cycle <i>ME (Brenda Ueland)</i> by Libby Larsen.

Brenda Ueland, a free-lance writer, journalist, mother, teacher and feminist, lived for nearly a century. During her life, Ueland wrote two books: If You Want to Write: A Book about Art, Independence and Spirit, published in 1938, and an autobiography, Me: Brenda Ueland, published in 1939. In 1987, American composer Libby Larsen chose excerpts from Ueland's autobiography to serve as texts for a cycle of eight songs that represent episodic periods of Ueland's life. This study compares Ueland's autobiography to that of Libby Larsen's song cycle Me (Brenda Ueland). The order in which the text appeared in the song cycle was quite different from that of the memoir, and pivotal areas of Ueland's life are not included, most significantly, her daughter Gaby, and the life and death of Ueland's sister-in-law Julie. These and other discrepancies are discussed, as well as the instances in which the song cycle complements the book. A few examples are cited regarding the ways in which knowing the autobiography in its complete form may affect the dramatic presentation of the song cycle

HOST FACTORS CONTROLLING VIRUS INFECTION: IMPLICATIONS FOR ANTIVIRALS AND VIROTHERAPY

Viruses are obligate intracellular parasites rely heavily on host components and pathways for their replication. Studying different cellular factors affecting viral infection can enable us to identify novel drug targets, improve current antiviral treatments and improve efficacy of virus based therapies. This dissertation examines two prototypic members of an order Mononegavirales, vesicular stomatitis virus (VSV) and Sendai virus (SeV) and is focused on: 1) resistance of some hosts to a broad spectrum antiviral drug ribavirin and 2) resistance of some pancreatic cancers to oncolytic virotherapy. Here, for the first time we examined whether certain cell types are naturally resistant to ribavirin even without prior drug exposure. Our results show striking differences between cell types in their response to ribavirin. Our data also suggest that this resistance was due to cellular factors rather than viral determinants and ribavirin may inhibit the same virus via different mechanisms in different cells depending on the ribavirin metabolism. Additionally, resistance of oncolytic VSV therapy in specific human pancreatic ductal adenocarcinoma (PDA) cells was investigated and this resistance was attributed to constitutive expression of the IFN-stimulated antiviral genes MxA and OAS. Decreasing the levels of MxA and OAS by inhibition of JAK/STAT signaling, improved VSV infection and oncolysis. Overall, our study demonstrated heterogeneity in the type I IFN signaling status of PDA cells and suggests MxA and OAS as potential biomarkers for PDA resistance to VSV and other oncolytic viruses (OVs) sensitive to type I IFN responses

Calcium and phosphorus retention in frozen okra and spinach cooked in a steam jacketed kettle, a low-pressure steamer, and a high-pressure steamer

This study was conducted to determine the retention of calcium and of phosphorus in frozen okra and spinach cooked in a steam jacketed kettle, a low-pressure steamer, and a high-pressure steamer. Frozen institutional packages, each weighing 3 pounds, of okra and of spinach were obtained from a local wholesale food company. The vegetables were cooked according to the times recommended by the manufacturers of the equipment used in the study. When cooking times were not available for a particular vegetable, the times were established by preliminary tests. Samples of cooked and uncooked okra and spinach were taken from individual packages and were ashed with nitric and perchloric acids on a hot plate. The ashed samples were transferred to volumetric flasks and were diluted with distilled water. Appropriate aliquots of the diluted samples were analyzed for calcium and for phosphorus

Home improvements in Durham, North Carolina, during years 1959-68

The objectives were to determine the forms of improvement made to exciting single dwelling structures, to identify the extent to which each form of improvement was utilized, to develop a cost classification, and to identify trends in home improvement in Durham, North Carolina, during the years 1959-1968. Data were collected from a 50% systematic sample of building permits issued by the Inspection Division of the city. Types of home improvement were classified as repairs, replacement, additions, alterations, conversion, and relocation. Findings of the study showed that on an average, 648 permits were issued per year. The largest amount of money was spent for alterations; the average home improvement cost per permit was $1,172. Cost classification indicated that as the amount of money spent increased, the number of permits issued for each type of improvement decreased. The greatest number of home improvements, regardless of type, were for general improvements and changes in porches. The greatest number of permits were issued for the downtown area of the city, whereas, the largest amount of money was spent in the southwest section

Protection of HepG2 cells from acrolein toxicity by CDDO-Im via glutathione-mediated mechanism

Acrolein is an environmental toxicant, mainly found in smoke released from incomplete combustion of organic matter. The compound is ubiquitously found in endogenous as well as exogenous environment. Several studies showed that exposure to acrolein can lead to liver damage. The mechanisms involved in acrolein-induced hepatocellular toxicity, however, are not completely understood. This study examines the toxic effects and cytotoxic mechanisms of acrolein on HepG2 cells. Acrolein at pathophysiological concentrations was shown to cause a concentration-dependent decrease in cell viability as measured by MTT and LDH assays. Acrolein exposure was also found to cause apoptotic cell death and an increase in levels of protein carbonyl and TBARS, markers of protein damage and lipid peroxidation, respectively, in HepG2 cells. Acrolein also rapidly depleted intracellular glutathione (GSH), phase II enzyme GSH-linked glutathione-S-transferases (GST) and aldose reductase (AR) -- three critical cellular defenses that detoxify reactive aldehydes. Results further showed that depletion of cellular GSH by acrolein preceded the loss of cell viability, which suggests that cellular GSH depletion may be an important event in acrolein-induced cytotoxicity. To further determine the role of cellular GSH in protecting against acrolein-mediated cytotoxicity, buthionine sulfoximine (BSO) was used to inhibit cellular GSH biosynthesis. It was observed that depletion of cellular GSH by BSO led to a marked potentiation of acrolein-mediated cytotoxicity in HepG2cells. Furthermore, induction of GSH levels by CDDO-Im, a triterpenoid compound, afforded protection against acrolein toxicity in a concentration-dependent manner. Notably, incubation of HepG2 cells with CDDO-Im at a concentration as low as 10 nM leads to a significant increase in GSH content. To further determine the role of GSH in CDDO-Im-mediated cytoprotection against acrolein-mediated cytotoxicity, BSO was used to inhibit cellular GSH induction by CDDO-Im. Pretreatment of HepG2 cells with BSO and CDDO-Im significantly inhibited CDDO-Im-mediated induction in cellular GSH levels and also reversed cytoprotective effects of CDDO-Im on acrolein-mediated toxicity. In summary, this study demonstrates that exposure to acrolein results in a faster depletion of GSH, an important phase II defense, and causes an increase in apoptosis, lipid peroxidation and protein carbonylation. Furthermore, the endogenous antioxidant GSH can be induced by CDDO-Im. The CDDO-Im-mediated elevated GSH appears to afford a marked protection against acrolein toxicity suggesting that GSH plays a predominant role in CDDO-Im-mediated protection against acrolein-induced toxicity in HepG2 cells. This study may provide understanding on the molecular action of acrolein which may be important to develop novel strategies for the prevention of acrolein-mediated toxicity