6 resultados para stress factors

em CORA - Cork Open Research Archive - University College Cork - Ireland


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Duchenne Muscular Dystrophy (DMD) is a fatal multi-system neuromuscular disease caused by loss of dystrophin. The loss of dystrophin from membranes of contractile muscle cells and the dysregulation of the DAPC, induces chronic inflammation due to tissue necrosis and eventual replacement with collagen which weakens muscular force and strength. Dystrophin deficiency may cause under-diagnosed features of DMD include mood disorders such as depression and anxiety and dysfunction of the gastrointestinal tract. The first study in the thesis examined mood in the dystrophin-deficient mdx mouse model of DMD and examined the effects of the tri-cyclic antidepressant, amitriptyline on behaviours. Amitriptyline had anti-depressant and anxiolytic effects in the mdx mice possibly through effects on stress factors such as corticotrophin-releasing factor (CRF). This antidepressant also reduced skeletal muscle inflammation and caused a reduction in circulating interleukin (IL)-6 levels. In the second and third studies, we specifically blocked IL-6 signalling and used Urocortin 2, CRFR2 agonist to investigate their potential as therapeutic targets in mdx mice pathophysiology. Isometric and isotonic contractile properties of the diaphragm, were compared in mdx mice treated with anti IL-6 receptor antibodies (anti IL-6R) and/or Urocortin 2. Deficits in force production, work and power detected in mdx mice were improved with treatment. In study three I investigated contractile properties in gastrointestinal smooth muscle. As compared to wild type mice, mdx mice had slower faecal transit times, shorter colons with thickened muscle layers and increased contractile activity in response to recombinant IL-6. Blocking IL-6 signalling resulted in an increase in colon length, normalised faecal output times and a reduction in IL-6-evoked contractile activity. The findings from these studies indicate that for both diaphragm and gastrointestinal function in a dystrophin-deficient model, targeting of IL-6 and CRFR2 signalling has beneficial therapeutic effects.

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The response of Lactococcus lactis subsp. cremoris NCDO 712 to low water activity (aw) was investigated, both in relation to growth following moderate reductions in the aw and in terms of survival following substantial reduction of the aw with NaCI. Lc.lactis NCDO 712 was capable of growth in the presence of ≤ 4% w/v NaCI and concentrations in excess of 4% w/v were lethal to the cells. The presence of magnesium ions significantly increased the resistance of NCDO 712 to challenge with NaCI and also to challenge with high temperature or low pH. Survival of Lc.lactis NCDO 712 exposed to high NaCI concentrations was growth phase dependent and cells were most sensitive in the early exponential phase of growth. Pre-exposure to 3% w/v NaCI induced limited protection against subsequent challenge with higher NaCI concentrations. The induction was inhibited by chloramphenicol and even when induced, the response did not protect against NaCI concentrations> 10% w/v. When growing at low aw, potassium was accumulated by Lc. lactis NCDO 712 growing at low aw, if the aw was reduced by glucose or fructose, but not by NaCI. Reducing the potassium concentration of chemically defined medium from 20 to 0.5 mM) produced a substantial reduction in the growth rate, if the aw was reduced with NaCI, but not with glucose or fructose. The reduction of the growth rate correlated strongly with a reduction in the cytoplasmic potassium concentration and in cell volume. Addition of the compatible solute glycine betaine, partially reversed the inhibition of growth rate and partially restored the cell volume. The potassium transport system was characterised in cells grown in medium at both high and low aw. It appeared that a single system was present, which was induced approximately two-fold by growth at low aw. Potassium transport was assayed in vitro using cells depleted of potassium; the assay was competitively inhibited by Na+ and by the other monovalent cations NH4+, Li+, and Cs+. There was a strong correlation between the ability of strains of Lc. lactis subsp. lactis and subsp. cremoris to grow at low aw and their ability to accumulate the compatible solute glycine betaine. The Lc. lactis subsp. cremoris strains incapable of growth at NaCI concentrations> 2% w/v did not accumulate glycine betaine when growing at low aw, whereas strains capable of growth at NaCI concentrations up to 4% w/v did. A mutant, extremely sensitive to low aw was isolated from the parent strain Lc. lactis subsp. cremoris MG 1363, a plasmid free derivative of NCDO 712. The parent strain tolerated up to 4% w/v NaCI and actively accumulated glycine betaine when challenged at low aw. The mutant had lost the ability to accumulate glycine betaine and was incapable of growth at NaCI concentrations >2% w/v or the equivalent concentration of glucose. As no other compatible solute seemed capable of substitution for glycine betaine, the data suggest that the traditional; phenotypic speciation of strains on the basis of tolerance to 4% w/v NaCI can be explained as possession or lack of a glycine betaine transport system.

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This study explores the experiences of stress and burnout in Irish second level teachers and examines the contribution of a number of individual, environmental and health factors in burnout development. As no such study has previously been carried out with this sample, a mixed-methods approach was adopted in order to comprehensively investigate the subject matter. Teaching has consistently been identified as a particularly stressful occupation and research investigating its development is of great importance in developing measures to address the problem. The first phase of study involved the use of focus groups conducted with a total of 20 second-level teachers from 11 different schools in the greater Cork city area. Findings suggest that teachers experience a variety of stressors – in class, in the staff room and outside of school. The second phase of study employed a survey to examine the factors associated with burnout. Analysis of 192 responses suggested that burnout results from a combination of demographic, personality, environmental and coping factors. Burnout was also found to be associated with a number of physical symptoms, particularly trouble sleeping and fatigue. Findings suggest that interventions designed to reduce burnout must reflect the complexity of the problem and its development. Based on the research findings, interventions that combine individual and organisational approaches should provide the optimal chance of effectively tackling burnout.

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Existing work in Computer Science and Electronic Engineering demonstrates that Digital Signal Processing techniques can effectively identify the presence of stress in the speech signal. These techniques use datasets containing real or actual stress samples i.e. real-life stress such as 911 calls and so on. Studies that use simulated or laboratory-induced stress have been less successful and inconsistent. Pervasive, ubiquitous computing is increasingly moving towards voice-activated and voice-controlled systems and devices. Speech recognition and speaker identification algorithms will have to improve and take emotional speech into account. Modelling the influence of stress on speech and voice is of interest to researchers from many different disciplines including security, telecommunications, psychology, speech science, forensics and Human Computer Interaction (HCI). The aim of this work is to assess the impact of moderate stress on the speech signal. In order to do this, a dataset of laboratory-induced stress is required. While attempting to build this dataset it became apparent that reliably inducing measurable stress in a controlled environment, when speech is a requirement, is a challenging task. This work focuses on the use of a variety of stressors to elicit a stress response during tasks that involve speech content. Biosignal analysis (commercial Brain Computer Interfaces, eye tracking and skin resistance) is used to verify and quantify the stress response, if any. This thesis explains the basis of the author’s hypotheses on the elicitation of affectively-toned speech and presents the results of several studies carried out throughout the PhD research period. These results show that the elicitation of stress, particularly the induction of affectively-toned speech, is not a simple matter and that many modulating factors influence the stress response process. A model is proposed to reflect the author’s hypothesis on the emotional response pathways relating to the elicitation of stress with a required speech content. Finally the author provides guidelines and recommendations for future research on speech under stress. Further research paths are identified and a roadmap for future research in this area is defined.

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HFE is a transmembrane protein that becomes N-glycosylated during transport to the cell membrane. It acts to regulate cellular iron uptake by interacting with the Type 1 transferrin receptor and interfering with its ability to bind iron-loaded transferrin. There is also evidence that HFE regulates systemic iron levels by binding to the Type II transferrin receptor although the mechanism by which this occurs is still not well understood. Mutations to HFE that disrupt this function, or physiological conditions that decrease HFE protein levels, are associated with increased iron uptake, and its accumulation in tissues and organs. This is exemplified by the point mutation that results in conversion of cysteine residue 282 to tyrosine (C282Y), and gives rise to the majority of HFE-related hemochromatoses. The C282Y mutation prevents the formation of a disulfide bridge and disrupts the interaction with its co-chaperone β2-microglobulin. The resulting misfolded protein is retained within the endoplasmic reticulum (ER) where it activates the Unfolded Protein Response (UPR) and is subjected to proteasomal degradation. The absence of functional HFE at the cell surface leads to unregulated iron uptake and iron loading. While the E3 ubiquitin ligase involved in the degradation of HFE-C282Y has been identified, the mechanism by which it is targeted for degradation remains relatively obscure. The primary objective of this project was to further our understanding of how the iron regulatory HFE protein is targeted for degradation. Our studies suggest that the glycosylation status, and the active process of deglycosylation, are central to this process. We identified a number of additional factors that can contribute towards degradation and explored their regulation during ER stress conditions.

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Background: This study examines perceived stress and its potential causal factors in nurses. Stress has been seen as a routine and accepted part of the healthcare worker’s role. The lack of research on stress in nurses in Ireland motivated this study. Aims: The aims of this study are to examine the level of stress experienced by nurses working in an Irish teaching hospital, and investigate differences in perceived stress levels by ward area and associations with work characteristics. Method: A cross-sectional study design was employed, with a two-stage cluster sampling process. A self-administered questionnaire was used to collect the data and nurses were investigated across ten different wards using the Nursing Stress Scale and the Demand Control Support Scales. Results: The response rate was 62%. Using outpatients as a reference ward, perceived stress levels were found to be significantly higher in the medical ward, accident and emergency, intensive care unit and paediatric wards (p<0.05). There was no significant difference between the wards with regard to job strain, however, differences did occur with levels of support; the day unit and paediatric ward reporting the lowest level of supervisor support (p<0.01). A significant association was seen between the wards and perceived stress even after adjustment (p<0.05). Conclusion: The findings suggest that perceived stress does vary within different work areas in the same hospital. Work factors, such as demand and support are important with regard to perceived stress. Job control was not found to play an important role.