Thesis (Ph. D.)--Virginia Commonwealth University, 2006. / Prepared for: Dept. of Psychology. Bibliography: leaves 78-90. Also available online via the Internet.

Thesis (Ph. D.)--Auburn University. / Abstract. Vita. Includes bibliographical references (p. 111-128).

Thesis (Ph. D.)--University of Missouri-Columbia, 1996. / Typescript. Vita. Includes bibliographical references (leaves 120-134). Also available on the Internet.

Thesis (Ph. D.)--University of Missouri-Columbia, 1996. / Typescript. Vita. Includes bibliographical references (leaves 120-134). Also available on the Internet.

The adverse effects of exposure to unrealistic ideals in the media are well documented, however, this is the first study to explore the possibility that women may experience improvement in body image and affect via social comparison to women with realistic, non-ideal body shape and size. Using material from The Century Project©, the impact of exposure to nude, non-pornographic photographs of women of varied shape, size, age, and physical condition, and the photographed women's personal commentaries about how they successfully cope with body image concerns was tested using an experimental design. It was hypothesized that exposure to the photographs and their associated commentaries would lead to an improvement in body image, mood, and self-esteem, and that this effect would be moderated by preexisting levels of internalization of the thin ideal and strong core beliefs about the importance of appearance (schematicity). Women exposed to the photos and comments condition experienced significantly less appearance-related anxiety than those exposed to photo-only and comments-only conditions, and internalization, but not schematicity, moderated this effect. Findings suggest women who have a greater tendency to internalize sociocultural body image standards may be more receptive to positive changes in these standards when presented with a persuasive visual and cognitive stimulus. However, without both aspects (visual and commentary) high internalizers appear to experience greater negative reactions to these stimuli.

In the U.K. deaths due to liver diseases, especially alcohol related diseases, have risen considerably over the last 20 years. In 2005 up to 13,000 people died from liver related diseases within the U.K., including alcohol and viral liver failure and liver cancers. Worldwide hepatitis B affects about 2 billion people, killing 500,000 to 1 million per year. An effective way to treat liver disease is often liver surgery, such as liver resection for cancers and liver transplant for failure. However, the failure of liver regeneration by hepatocyte proliferation after resection surgery leads to a high death rate, and a shortage of liver donors means most people with liver failure die without access to a transplant. Therefore, understanding hepatocyte proliferation is a key to improving survival after resection surgery and providing hepatocytes for cell therapy in place of organ donation. The mechanism of hepatocyte proliferation has been studied both in vivo and in culture by many groups. However, only limited proliferation and preservation of function of primary human and rat hepatocytes, not suitable for clinical use, has been achieved on stimulation with growth factors. This study focuses on the mechanism of epidermal growth factor (EGF) stimulation of rat hepatocyte cell cycle progression and proliferation, including the role of PI3K/Akt/mTOR and MEK/ERK signalling pathways, EGF receptor location after activation of downstream proteins such as protein kinase B (Akt) and extracellular signal-regulated kinases 1/2 (ERK1/2), and their effect on the cell cycle. Included in this study are some comparisons between the stimulation of the EGF receptor (a tyrosine kinase receptor) and the P2Y receptor (a G protein coupled receptor). The PI3K/Akt/mTOR signalling pathway appears to be necessary for the hepatocyte response to EGF, inducing progression to S phase and DNA synthesis, while the MEK/ERK pathway is important but not necessary. The P2Y2 agonist UTP, which also stimulates these two pathways, does not result in the cell entering S phase. This suggests that the activation of these two signalling pathways is not sufficient for cell cycle progression. Furthermore, infection of cells with adenovirus to express constitutively active Akt increases hepatocytes proliferation and induces cell cycle progression, which generates a window to obtain hepatocytes proliferation in culture. It has been shown in this thesis that EGF stimulation of ERK phosphorylation continues from endosomes, while the evidence suggests that UTP stimulation is restricted to signalling at the cell surface. Furthermore, endocytic EGF/EGFR alone (without stimulation from the cell surface) is sufficient to induce cell cycle progression. This endosomal signalling with EGF but not UTP may explain the absence of cell cycle progression following UTP. EGF stimulates the appearance of phospho-EGFR in the nucleus. Furthermore, nuclear EGFR has a different apparent molecule weight than the cytoplasmic receptor; this may be due to nuclear EGFR having fewer and/or different phosphates. In vivo work by others has shown that in liver regeneration following partial hepatectomy (PH) EGF and full-length activated-EGFR were showed to be present in proliferating hepatocytes. This thesis describes the mechanism of growth factor (EGF) stimulation of primary rat hepatocyte proliferation. It shows for the first time that endosomal EGF/EGFR alone is sufficient to stimulate cell cycle progression, and that EGF induces phospho-EGFR in the nucleus in cultured rat hepatocytes. This thesis also provides the possibility to obtain cultured hepatocytes proliferation including over-expression of constitutively active form of Akt and translocation to the nucleus of full-length EGFR in the phosphorylated form. These studies improve our understanding of growth factor (e.g. EGF) stimulation of hepatocyte proliferation in vitro and help to move closer to the goal of obtaining sufficient functional hepatocytes in culture for clinical use, and of drugs that will stimulate hepatocyte proliferation following resection surgery.

Laminin binding integrins 6 (CD49f) and 3 (CD49c) are persistently but differentially expressed in prostate cancer (PCa). Integrin internalization is an important determinant of their cell surface expression and function. Using flow cytometry, and first order kinetic modeling, we quantitated the intrinsic internalization rates of integrin subunits in a single cycle of internalization. In PCa cell line DU145, 6 integrin internalized with a rate constant (k(actual)) of 3.25min(-1), threefold faster than 3 integrin (1.0min(-1)), 1.5-fold faster than the vitronectin binding v integrin (CD51) (2.2min(-1)), and significantly slower than the unrelated transferrin receptor (CD71) (15min(-1)). Silencing of 3 integrin protein expression in DU145, PC3, and PC3B1 cells resulted in up to a 1.71-fold increase in k(actual) for 6 integrin. The internalized 6 integrin was targeted to early endosomes but not to lamp1 vesicles. Depletion of 3 integrin expression resulted in redistribution of 64 integrin to an observed cell-cell staining pattern that is consistent with a suprabasal distribution observed in epidermis and early PIN lesions in PCa. Depletion of 3 integrin increased cell migration by 1.8-fold, which was dependent on 61 integrin. Silencing of 6 integrin expression however, had no significant effect on the k(actual) of 3 integrin or its distribution in early endosomes. These results indicate that 3 and 6 integrins have significantly different internalization kinetics and that coordination exists between them for internalization. J. Cell. Biochem. 118: 1038-1049, 2017.

Salmonella outbreaks associated with orange juices have been reported in the past. Though there have been studies on the internalization of Salmonella into oranges there is inadequate information on the ability of this pathogen to survive on orange surfaces, become internalized, and survive the low pH internal conditions. The objective of this work was to study the survival of Salmonella gaminara and Salmonella agona on oranges obtained from the field and retail outlets and investigate their attachment and internalization potential. These studies showed that oranges obtained from both the field and retail outlets harbored relatively high concentrations of aerobic heterotrophic bacterial populations. There were significant differences in the survival of Salmonella agona and Salmonella gaminara at 4??C, room temperature (25??C) and 37??C. Survival was highest at 37??C and lowest at 4??C for both Salmonella gaminara and Salmonella agona. Salmonella agona and Salmonella gaminara showed significant differences in recovery when the cells were treated with pH 4.0, 7.0 and 9.5 buffers. The internalization studies suggest that a negative temperature differential favors the internalization of Salmonella cells into the fruit. Significant differences in the internalization of Salmonella into field and market oranges were observed with more internalization in the field oranges as compared to the market oranges. These results suggest that to prevent Salmonella contamination of orange juices adequate pre-harvest protection against pathogen contamination and post-harvest cleaning and disinfection strategies need to be employed.

Salmonella outbreaks associated with orange juices have been reported in the past. Though there have been studies on the internalization of Salmonella into oranges there is inadequate information on the ability of this pathogen to survive on orange surfaces, become internalized, and survive the low pH internal conditions. The objective of this work was to study the survival of Salmonella gaminara and Salmonella agona on oranges obtained from the field and retail outlets and investigate their attachment and internalization potential. These studies showed that oranges obtained from both the field and retail outlets harbored relatively high concentrations of aerobic heterotrophic bacterial populations. There were significant differences in the survival of Salmonella agona and Salmonella gaminara at 4??C, room temperature (25??C) and 37??C. Survival was highest at 37??C and lowest at 4??C for both Salmonella gaminara and Salmonella agona. Salmonella agona and Salmonella gaminara showed significant differences in recovery when the cells were treated with pH 4.0, 7.0 and 9.5 buffers. The internalization studies suggest that a negative temperature differential favors the internalization of Salmonella cells into the fruit. Significant differences in the internalization of Salmonella into field and market oranges were observed with more internalization in the field oranges as compared to the market oranges. These results suggest that to prevent Salmonella contamination of orange juices adequate pre-harvest protection against pathogen contamination and post-harvest cleaning and disinfection strategies need to be employed.

Ligand-induced internalisation and subsequent downregulation of receptor tyrosine kinases (RTKs) serve to determine biological outputs of their signalling. Intrinsically kinase-deficient RTKs control a variety of biological responses, however, the mechanism of their downregulation is not well understood and its analysis is focused exclusively on the ErbB3 receptor. The Eph group of RTKs is represented by the EphA and EphB subclasses. Each bears one kinase-inactive member, EphA10 and EphB6, respectively, suggesting an important role for these molecules in the Eph signalling network. While EphB6 effects on cell behaviour have been assessed, the mechanism of its downregulation remains elusive. Our work reveals that EphB6 and its kinase-active relative, and signaling partner, EphB4, are downregulated in a similar manner in response to their common ligand, ephrin-B2. Following stimulation, both receptors are internalised through clathrin-coated pits and are degraded in lysosomes. Their targeting for lysosomal degradation relies on the activity of an early endosome regulator, the Rab5 GTPase, as this process is inhibited in the presence of a Rab5 dominant-negative variant. EphB6 also interacts with the Hsp90 chaperone and EphB6 downregulation is preceded by their rapid dissociation. Moreover, the inhibition of Hsp90 results in EphB6 degradation, mimicking its ligand-induced downregulation. These processes appear to rely on overlapping mechanisms, since Hsp90 inhibition does not significantly enhance ligand-induced EphB6 elimination. Taken together, our observations define a novel mechanism for intrinsically kinase-deficient RTK downregulation and support an intriguing model, where Hsp90 dissociation acts as a trigger for ligand-induced receptor removal.