Wrapping Snakes for Improved Lip Segmentation

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Edinburgh Napier University Research Safeguarding Framework

This guidance document outlines the policy and support framework for research and innovation activities through which the commitment of the University in its obligation to protect children and adults who are at risk of harm, abuse, neglect, exploitation, or discrimination is set out. This guide uses the term ‘safeguarding’ in its widest possible sense throughout

Edinburgh Napier University Research Safeguarding Framework

This guidance document outlines the policy and support framework for research and innovation activities through which the commitment of the University in its obligation to protect children and adults who are at risk of harm, abuse, neglect, exploitation, or discrimination is set out. This guide uses the term ‘safeguarding’ in its widest possible sense throughout

Expression of pro-inflammatory proteins in the lung epithelial cell line A549, in response to cytokine, and environmental particle exposure

This thesis investigates the effects of various inflammatory stimuli, including cytokines and air pollution particles, on the expression and secretion of various proinflammatory proteins in the lung epithelial cell line A549. The pro-inflammatory proteins investigated were C-reactive protein (CRP), fibrinogen, and heat shock protein 70 (Hsp70), all of which are known to be produced during inflammation and are also known risk factors for cardiovascular disease. These proteins were investigated because inhalation of particulate air pollution has been associated with increased cardiovascular disease and mortality. The production of these proteins in the lung may be involved in a systemic inflammatory response which increases the plasma levels of these proteins and other cardiovascular risk factors therefore increasing the susceptibility for cardiovascular events. Alternatively, localised CRP functions as an opsonin, while fibrinogen and its degradation products are involved in the recruitment of neutrophils and leukocytes to the lung. Both CRP and fibrinogen are known to be produced in hepatocytes in response to cytokines. Chapter 3 investigates the effect of cytokine treatment of the A549 cells which shows that CRP and fibrinogen can be induced in this cell line by various cytokines. CRP was found to be induced by the cytokines ILI P, EL6, IL8, TNF(x and IFN7 with increased effects shown by simultaneous treatment with two cytokines. Fibrinogen was found to be induced mainly by IL6, but fibrinogen levels were also slightly increased by ILlp; simultaneous treatments of IL6 with either ILlP or TNF(x reduced the effect of IL6 treatment. Treatment of A549 cells with IL6 and IL8 simultaneously induced a synergistic effect. After establishing that cytokines induce the expression of CRP in A549 cells, the effects of particulate air pollution on pro-inflammatory protein expression were then investigated (chapter 4). The cells were treated with carbon black (CB), ultrafine CB (ufCB), and iron chloride (FeC13) to find out what effect these air pollution components and PM10 would have on the expression of CRP, fibrinogen, Hsp70 and the transcription factor NFKB and its inhibitor IKB. NFKB is known be activated by PM10 and is involved in the signalling of pro-inflammatory responses. All the particulate treatments induced a pro-inflammatory response with expression and secretion of CRP, fibrinogen, and Hsp70, whereas the soluble metal treatment had little effect. The metal salt FeC13w as used to treat the cells since it has been suggested that PM10 may mediate its effect through the presence of transition metals which are implicated in oxidant generation. The particulate exposures were also associated with the activation and nuclear translocation of NFKB indicating the involvement of NFKB and IxB in the induction of the pro-inflammatory response. Investigations into the mechanisms by which the particles induced the proinflammatory response are discussed in chapter 5. Firstly, investigations into the effect of particles on the secretion of the pro-inflammatory proteins were carried out; these indicated that particles were capable of inducing the secretion of CRP, flbrinogen and Hsp70. Investigations into the transcriptional mechanisms of proinflammatory protein expression were carried out using specific inhibitors. CRP and fibrinogen were induced in an NFKB dependent manner, while Hsp70 was produced as a result of activation of the JAK/STAT pathway. The effect of oxidative stress being induced as a result of particle exposure was investigated using antioxidants. This showed a reduction in the amount of intracellular and secreted CRP, fibrinogen and Hsp70 in the presence of antioxidants, indicating that oxidative stress was involved. This correlated with a reduction in the levels of intracellular ATP. Finally in chapter 6 the effects of proteins secreted from A549 cells on the monocytelike cell line MM6 were examined. This was carried out as a model of the effects of secreted pro-inflammatory proteins from the lung epithelium on other cells. It was found that CRP and fibrinogen were able to induce the activation of NFkB in MM6 cells, indicating that secretion of these proteins during lung inflammation could have an effect on other resident lung cells. Conditioned medium from A549 cells was also found to induce the expression of pro-inflammatory proteins including CRP, fibrinogen, Hsp70, IL6, IL8 and TNFcc. The A549 conditioned medium also appeared to induce a stress response and cellular damage in MM6 cells, thereby potentially exacerbating the inflammatory response. These results indicate that pro-inflammatory proteins can be produced in lung epithelial cells in response to particle exposure as a result of oxidative stress. They may be involved in the progression of localised lung inflammation and in the systemic response to particulate air pollution.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Integrins and extracellular matrix in mechanotransduction

Integrins are a family of cell surface receptors which mediate cell–matrix and cell–cell adhesions. Among other functions they provide an important mechanical link between the cells external and intracellular environments while the adhesions that they form also have critical roles in cellular signal-transduction. Cell–matrix contacts occur at zones in the cell surface where adhesion receptors cluster and when activated the receptors bind to ligands in the extracellular matrix. The extracellular matrix surrounds the cells of tissues and forms the structural support of tissue which is particularly important in connective tissues. Cells attach to the extracellular matrix through specific cell-surface receptors and molecules including integrins and transmembrane proteoglycans. Integrins work alongside other proteins such as cadherins, immunoglobulin superfamily cell adhesion molecules, selectins, and syndecans to mediate cell–cell and cell–matrix interactions and communication. Activation of adhesion receptors triggers the formation of matrix contacts in which bound matrix components, adhesion receptors, and associated intracellular cytoskeletal and signaling molecules form large functional, localized multiprotein complexes. Cell–matrix contacts are important in a variety of different cell and tissue properties including embryonic development, inflammatory responses, wound healing, and adult tissue homeostasis. This review summarizes the roles and functions of integrins and extracellular matrix proteins in mechanotransduction

Expression of pro-inflammatory proteins in the lungepithelial cell line A549, in response to cytokine, andenvironmental particle exposure.

This thesis investigates the effects of various inflammatory stimuli, including cytokines and air pollution particles, on the expression and secretion of various proinflammatory proteins in the lung epithelial cell line A549. The pro-inflammatory proteins investigated were C-reactive protein (CRP), fibrinogen, and heat shock protein 70 (Hsp70), all of which are known to be produced during inflammation andare also known risk factors for cardiovascular disease. These proteins were investigated because inhalation of particulate air pollution has been associated with increased cardiovascular disease and mortality. The production of these proteins in the lung may be involved in a systemic inflammatory response which increases the plasma levels of these proteins and other cardiovascular risk factors thereforeincreasing the susceptibility for cardiovascular events. Alternatively, localised CRP functions as an opsonin, while fibrinogen and its degradation products are involved in the recruitment of neutrophils and leukocytes to the lung.Both CRP and fibrinogen are known to be produced in hepatocytes in response to cytokines. Chapter 3 investigates the effect of cytokine treatment of the A549 cellswhich shows that CRP and fibrinogen can be induced in this cell line by various cytokines. CRP was found to be induced by the cytokines ILI b, IL6, IL8, TNF(a and IFN7 with increased effects shown by simultaneous treatment with two cytokines. Fibrinogen was found to be induced mainly by IL6, but fibrinogen levels were alsoslightly increased by ILlb; simultaneous treatments of IL6 with either ILlb or TNF(a reduced the effect of IL6 treatment. Treatment of A549 cells with IL6 and IL8 simultaneously induced a synergistic effect.After establishing that cytokines induce the expression of CRP in A549 cells, the effects of particulate air pollution on pro-inflammatory protein expression were then investigated (chapter 4). The cells were treated with carbon black (CB), ultrafine CB (ufCB), and iron chloride (FeC13) to find out what effect these air pollution components and PM10 would have on the expression of CRP, fibrinogen, Hsp70 and the transcription factor NFKB and its inhibitor IKB. NFKB is known be activated by PM10 and is involved in the signalling of pro-inflammatory responses. All the particulate treatments induced a pro-inflammatory response with expression and secretion of CRP, fibrinogen, and Hsp70, whereas the soluble metal treatment had little effect. The metal salt FeC13w as used to treat the cells since it has been suggested that PM10 may mediate its effect through the presence of transition metals which are implicated in oxidant generation. The particulate exposures were also associated with the activation and nuclear translocation of NFKB indicating the involvement of NFKB and IxB in the induction of the pro-inflammatory response.Investigations into the mechanisms by which the particles induced the proinflammatory response are discussed in chapter 5. Firstly, investigations into the effect of particles on the secretion of the pro-inflammatory proteins were carried out; these indicated that particles were capable of inducing the secretion of CRP, flbrinogen and Hsp70. Investigations into the transcriptional mechanisms of proinflammatory protein expression were carried out using specific inhibitors. CRP and fibrinogen were induced in an NFKB dependent manner, while Hsp70 was produced as a result of activation of the JAK/STAT pathway. The effect of oxidative stress being induced as a result of particle exposure was investigated using antioxidants. This showed a reduction in the amount of intracellular and secreted CRP, fibrinogen and Hsp70 in the presence of antioxidants, indicating that oxidative stress was involved. This correlated with a reduction in the levels of intracellular ATP. Finally in chapter 6 the effects of proteins secreted from A549 cells on the monocytelike cell line MM6 were examined. This was carried out as a model of the effects of secreted pro-inflammatory proteins from the lung epithelium on other cells. It was found that CRP and fibrinogen were able to induce the activation of NFkB in MM6 cells, indicating that secretion of these proteins during lung inflammation could have an effect on other resident lung cells. Conditioned medium from A549 cells was also found to induce the expression of pro-inflammatory proteins including CRP, fibrinogen, Hsp70, IL6, IL8 and TNFcc. The A549 conditioned medium also appeared to induce a stress response and cellular damage in MM6 cells, thereby potentially exacerbating the inflammatory response.These results indicate that pro-inflammatory proteins can be produced in lung epithelial cells in response to particle exposure as a result of oxidative stress. They may be involved in the progression of localised lung inflammation and in the systemic response to particulate air pollution

Edinburgh Napier University Equality, Equity, Diversity and Inclusion in Research Framework

This framework the University expectations of equal opportunities on research and innovation (R&I) activities, funding and representation on funding decision panels. This is in line with the University Gender Equality Action Plan 2021-2025 and Race Equality Action Plan which commit to a positive environment where diversity and inclusiveness is celebrated and everyone is treated fairly regardless of sex, sexual orientation, gender reassignment, disability, age, ethnic origin, religion or belief, marital or civil partnership status or whether pregnant or on maternity leave

The application of phenotypic microarray analysis to anti-fungal drug development

Candida albicans metabolic activity in the presence and absence of acetylcholine was measured using phenotypic microarray analysis. Acetylcholine inhibited C. albicans biofilm formation by slowing metabolism independent of biofilm forming capabilities. Phenotypic microarray analysis can therefore be used for screening compound libraries for novel anti-fungal drugs and measuring antifungal resistance