Dissertations / Theses: 'BIOLOGICAL STRESS'

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Du, Plessis Keith R. (Keith Roland). "Biological indicators of copper-induced stress in soil." Thesis, Stellenbosch : Stellenbosch University, 2002. http://hdl.handle.net/10019.1/52719.

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Thesis (MSc)--University of Stellenbosch, 2002.
ENGLISH ABSTRACT: The concentrations of copper (Cu) in vineyard soils of the Western Cape range from 0.1 to 20 ppm. However, more than 160 tons of the fungicide copper oxychloride are annually being sprayed on these vineyards. This has raised concerns that Cu may accumulate in these soils, resulting in a negative impact on the soil biological processes, especially since the soils in the Western Cape are slightly acidic, making Cu more mobile and available for soil organisms than would have been the case in alkaline soils. The goal of the initial part of this study was therefore to identify those soil microbial communities indigenous to the Western Cape, which are most susceptible to Cu-induced stress as a result of the addition of copper oxychloride. These potential bioindicators of Cu-induced stress were first searched for in uncultivated agricultural soil from Nietvoorbij experimental farm. Consequently, a series of soil microcosms was prepared by adding various concentrations of Cu as a component of copper oxychloride, to each of eight aliquots of soil: 0 (control), 10, 20, 30, 40, 50, 100, 500 and 1000 ppm. The resulting concentrations of exchangeable Cu in these microcosms were found to be 2 (control), 12,23,34,42,59, 126,516 and 1112 ppm. Selected microbial communities in each microcosm were subsequently monitored over a period of 245 days. It was found that the culturable microbial numbers did not provide a reliable indication of the effect of Cu on community integrity. However, analyses of terminal-restriction fragment length polymorphism (T-RFLP) community fingerprints and especially analyses of the whole community metabolic profiles, revealed that shifts in the soil microbial communities took place as the Cu concentration increased. Direct counts of soil protozoa also revealed that the addition of Cu to the soil impacted negatively on the numbers of these eukaryotes. To confirm these findings in other soil ecosystems, the impact of copper oxychloride on whole community metabolic profiles and protozoan numbers were investigated in soils from Koopmanskloof commercial farm and Nietvoorbij experimental farm. These potential bioindicators were subsequently monitored in a series of soil microcosms prepared for each soil type by adding the estimated amounts of 0 (control), 30, 100 and 1000 ppm Cu as a component of copper oxychloride to the soil. The results confirmed the fmdings that elevated levels of copper impact negatively on the metabolic potential and protozoan numbers of soil. Consequently, it was decided to investigate a combination of protozoan counts and metabolic profiling as a potential bioindicator for Cu-induced stress in soil. Data collected from all the microcosms containing exchangeable Cu concentrations ranging from 1 ppm to 1112 ppm was used to construct a dendrogram using carbon source utilization profiles in combination with protozoan counts. It was found that the microcosms grouped into clusters, which correlated with the concentration of exchangeable Cu in the soil. Under the experimental conditions used in this study, the combination of protozoan counts and metabolic profiling seemed to be a reliable indicator of Cu-induced stress. However, this bioindicator must be further investigated in other soil types using other types of stress inducing pollutants. In addition to the above fmdings it was also found that the numbers of soil protozoa was particularly susceptible to Cu-induced stress in soils with a low soil pH. This is in agreement with the fmdings of others on the bio-availability of heavy metals in low pH soils. In these soils, nutrient cycling as a result of protozoan activity, may therefore be particularly susceptible to the negative impact of copper to the soil.
AFRIKAANSE OPSOMMING: Die konsentrasies van koper (Cu) in wingerdgronde van die Wes-Kaap wissel tussen 0.1 en 20 dpm. Meer as 160 ton van die fungisied koper-oksichloried word egter jaarliks op dié wingerde gespuit, wat kommer laat ontstaan het oor die moontlike akkumulasie van Cu in dié grond en die gevaar van 'n negatiewe impak op die biologiese prosesse in die grond. Die gevaar word vererger deur die feit dat die Wes-Kaapse grond effens suur is, wat Cu meer mobiel en beskikbaar maak vir grondorganismes as wat die geval sou wees in alkaliese grond. Die eerste doelstelling van hierdie studie was dus om die mikrobiese gemeenskappe in die grond, wat inheems is aan die Wes-Kaap, te identifiseer wat die meeste vatbaar is vir Cu-geïnduseerde stres as gevolg van die toevoeging van koper-oksichloried. Hierdie potensiële bioindikatore van Cu-geïnduseerde stres is eerstens gesoek in onbewerkte landbougrond van die Nietvoorbij-proefplaas. 'n Reeks grondmikrokosmosse is gevolglik berei deur verskillende konsentrasies Cu, as 'n komponent van koperoksichloried, by elk van agt hoeveelhede grond te voeg naamlik 0 (kontrole), 10,20, 30, 40, 50, 100, 500 en 1000 dpm. Die gevolglike konsentrasies van uitruilbare Cu in hierdie mikrokosmosse was 2 (kontrole), 12, 23, 34, 42, 59, 126, 516 en 1112 dpm. Geselekteerde mikrobiese gemeenskappe in elke mikrokosmos is vervolgens oor 'n tydperk van 245 dae bestudeer. Daar is gevind dat die kweekbare mikrobiese tellings nie 'n betroubare aanduiding kon gee van die uitwerking van Cu op gemeenskapsintegriteit nie. Die ontledings van terminale-restriksie fragment lengte polymorfisme (T-RFLP) gemeenskapsvingerafdrukke en veral van die metaboliese profiele van die totale gemeenskap, het getoon dat verskuiwings in die grondmikrobiese gemeenskappe plaasgevind het met 'n toename in Cu-konsentrasies. Direkte tellings van grondprotosoë het ook aangedui dat die toevoeging van Cu tot die grond 'n negatiewe uitwerking op die getalle van hierdie eukariote gehad het. Om dié resultate te bevestig, is die impak van koper-oksichloried op die metaboliese profiele van totale gemeenskappe en protosoë-getalle in ander grond-ekosisteme vervolgens bestudeer deur grond van die kommersiële plaas Koopmanskloof en die Nietvoorbij-proefplaas te gebruik. Dié potensiële bioindikatore is vervolgens bestudeer in 'n reeks grondmikrokosmosse, wat vir elke grondtipe voorberei is deur die toevoeging van beraamde hoeveelhede van 0 (kontrole), 30, 100 en 1000 dpm Cu as 'n komponent van koper-oksichloried. Die resultate het die bevindings bevestig dat verhoogde vlakke van Cu 'n negatiewe uitwerking het op die metaboliese potensiaal en op die protosoëgetalle in die grond. Daar is gevolglik besluit om 'n kombinasie van protosoë-tellings en metaboliese profiele te ondersoek as 'n potensiële bioindikator van Cu-geïnduseerde stres in grond. Data van al die mikrokosmosse wat uitruilbare Cu bevat, wisselend van 1 dpm tot 1112 dpm, is gebruik om 'n dendrogram te konstrueer wat koolstofbronbenuttingsprofiele in kombinasie met protosoë tellings gebruik. Daar is gevind dat die mikrokosmosse groepe vorm wat korrelleer met die konsentrasie uitruilbare Cu in die grond. Onder die eksperimentele kondisies wat in dié studie gebruik is, wil dit voorkom of die kombinasie van protosoë-tellings en metaboliese profiele 'n betroubare indikator van Cugeïnduseerde stres is. Hierdie bioindikator moet egter verder in ander grondtipes en met ander tipes stres-induserende besoedeling ondersoek word. By bogenoemde bevindings is daar ook gevind dat die getalle grondprotosoë besonder gevoelig is vir Cu-geïnduseerde stres in grond met In lae pH. Dit is in ooreenstemming met die bevindings van andere met betrekking tot die bio-beskikbaarheid van swaar metale in grond met 'n lae pH. In dié tipe grond mag nutriëntsiklering as gevolg van protosoë aktiwiteit besonder gevoelig wees vir die negatiewe uitwerking van koper in die grond.

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Karlsson, Louise. "Stress : From a biological, social, and psychological perspective." Thesis, Högskolan i Skövde, Institutionen för biovetenskap, 2018. http://urn.kb.se/resolve?urn=urn:nbn:se:his:diva-16104.

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Over the years stress has been a term lacking one clear and specific definition. In general, the term stress has been used mostly as an explanation of a response or reaction to a stressor. A stressor can be of both physiological and behavioral character. The experience of stress can occur both due to a real or a perceived stressor. In this literature review, the concept of stress is viewed with insights from biological, psychological, and social perspectives. The stress response is described biologically with the central nervous system (CNS), the brain, and the hypothalamic-pituitary-adrenal (HPA) axis. Social and psychological stress are concepts related to how stress is perceived by the mind and due to social surroundings which is described in relation to social support, self-efficacy, the locus of control and cognitive appraisal. Dealing with stress can be done through coping which refers to the individual capacity to handle a stressor and has generally been divided into two categories, active/passive coping and problem-focused/emotion-focused coping. Depending on the individual resources to cope with a stressor and the ability to decrease the stress response when needed, the long-term effects of stress can therefore vary between individuals. It has been found that positive coping (known as reducing stress) can increase the anterior cingulate cortex (ACC) volume and decrease anxiety and depression. The prefrontal cortex (PFC), the hippocampus, and the amygdala are closely linked to the ACC and affect emotions, learning, and memory related to the stress response.

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Hecht, Vivian (Vivian Chaya). "Biophysical responses of lymphocytes to environmental stress." Thesis, Massachusetts Institute of Technology, 2016. http://hdl.handle.net/1721.1/103693.

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Thesis: Ph. D., Massachusetts Institute of Technology, Department of Biological Engineering, 2016.
Cataloged from PDF version of thesis. "February 2016."
Includes bibliographical references (pages 139-151).
Cellular biophysical properties both reflect and influence cell state. These parameters represent the consequences of the interactions of multiple molecular events, and thus may reveal information otherwise obscured when measuring individual pathways in isolation. Previous work has demonstrated how precise measurements of certain of these properties, such as mass, volume, density and deformability using a suspended microchannel resonator (SMR) can help characterize cellular behavior and physiological role. Here, we expand upon this previous work to demonstrate the necessity of measuring multiple parameters simultaneously to fully determine cellular responses to environmental perturbations, and describe a situation in which changes to density and size promote survival under conditions of limited nutrient availability. We first investigate the relationship between cell density, volume, buoyant mass, and passage time through a narrow constriction under a variety of environmental stresses. Osmotic stress significantly affects density and volume, as previously shown. In contrast to density and volume, the effect of an osmotic challenge on passage time is relatively small. Deformability, determined by comparing passage times for cells with similar volume, exhibits a strong dependence on osmolarity, indicating that passage time alone does not always provide a meaningful proxy for deformability. Finally, we find that protein synthesis inhibition, cell cycle arrest, protein kinase inhibition, and cytoskeletal disruption result in unexpected relationships between deformability, density, and volume. Taken together, our results suggest that measuring multiple biophysical parameters can detect unique characteristics that more specifically reflect cellular behaviors. We next examine how cellular biophysical changes occurring immediately after growth factor depletion in lymphocytes promote adaptation to reduced nutrient uptake. We describe an acute biophysical response to growth factor withdrawal, characterized by a simultaneous decrease in cell volume and increase in cell density prior to autophagy initiation, observed in both FL5.12 cells depleted of IL-3 and primary CD8+ T cells depleted of IL-2 and differentiating towards memory cells. The response reduces cell surface area to minimize energy expenditure while conserving biomass, suggesting that the biophysical properties of cells can be regulated to promote survival under conditions of nutrient stress.
by Vivian Hecht.
Ph. D.

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Lamb, Angharad. "Mathematical Modelling of the Biological Stress Response to Chronium." Thesis, University of Nottingham, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.517846.

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Lu, Buyu. "Hormones of stress and control of adipocyte biological "colour"." Thesis, University of Warwick, 2011. http://wrap.warwick.ac.uk/46849/.

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The family of “stress” peptides that includes CRH and UCNs are emerging as important regulators of the homeostatic mechanisms regulating energy balance and metabolism. These peptides exert well documented central anorectic and thermogenic actions in controlling food uptake and optimise energy losses. Furthermore, CRH acting through specific G-protein coupled receptors, CRH-R1 and R2 can target multiple peripheral tissues such as skeletal muscle and adipose tissue to influence important metabolic pathways. Two types of adipose tissue exist in mammals: WAT and BAT. Since WAT is the largest energy reserve in mammals and BAT can utilize energy through adaptive thermogenesis, one of the goals in this study was to identify the presence of CRH system components in adipose tissue. Real time RT-PCR and immunofluorescence demonstrated that CRH-Rs as well as CRH, UCN-I, and UCN-II are expressed in both WAT and BAT, raising the possibility that CRH and UCNs are important regulators of energy storage and adaptive thermogenesis. Also the functional roles of CRH-Rs in adipose tissue were investigated. Using an experimental paradigm the T37i fibroblast that can differentiate into brown adipocyte, it was demonstrated that CRH at low (nanomolar) but not high (submicromolar) concentrations stimulated a signaling pathway involving the AC/cAMP/PKA/AMPK signaling cascade that regulates downstream phosphorylation of HSL. This was associated with a significant translocation of HSL toward lipid droplets and association with perilipin, as demonstrated with immunofluorescence. Studies applying quantitative RT-PCR also suggested that CRH-R1 appears to regulate genes important for adaptive thermogenesis, whereas CRH-R2 likely regulates brown adipocyte formation. Further analysis using an experimental paradigm the 3T3L1 fibroblast that can differentiate into white adipocyte showed that exposure of 3T3L1 cells to UCN-II (a specific CRH-R2 agonist) or NBI-27914 (a CRH-R1 specific antagonist) were able to induce morphological and biochemical characteristics suggesting adipocyte differentiation to a “beige” phenotype in white preadipocytes/adipocytes. Thus, CRH-R1 and R2 could be of potential importance in maintenance of energy homeostasis. Moreover, in vivo analysis showed that CRH system seems to demonstrate a certain degree of plasticity in response to stress perturbation. For instance, HFD significantly repressed the expression of CRH-Rs and their agonists, whereas food deprivation dramatically increased their expression. The analysis of quantitative RTPCR demonstrated that this activation of CRH system might be associated with induction of ‘beige’ cells in white fat depots. Since CRH-R1 KO mice displayed a lean phenotype and resistance to HFD-induced fat accumulation and these phenotypes can be reversed by supplementation of corticosterone, role of CRH-R2 in adipose tissue of these KO mice was investigated. Data showed that CRH-R2 activation likely induced BAT activity and transdifferentiation from WAT to BAT in CRH-R1 KO mice. Corticosterone reversed these changes in KO mice via potential suppression of CRH-R2.

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Erickson, Erika M. "The growth and stress response characterization of Synechococcus WH8109 cyanobacteria." Thesis, Massachusetts Institute of Technology, 2009. http://hdl.handle.net/1721.1/61214.

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Thesis (M. Eng.)--Massachusetts Institute of Technology, Dept. of Biological Engineering, 2009.
Cataloged from PDF version of thesis.
Includes bibliographical references (p. 60-64).
Oceanic cyanobacteria are amongst the most populous species on the planet and have been found in every ocean around the world. These photosynthetic organisms play a major role in the global carbon cycle. They have adapted to a number of different temperature, light, and nutrient niches. However, as important primary producers in the oceans, these organisms play a vital role which may be threatened by global climate change and pollution. As research on cyanobacterial species progresses, these organisms have been found to show promise as potential sources of biofuel, renewable energy, and agents for bioremediation. In order to utilize these organisms for future engineering applications and basic scientific research, it is important to be able to grow the organism in a stable and reproducible manner. This research characterizes the growth of Synechococcus WH8109 in the laboratory. In the laboratory, cell culture densities of greater than 109 cells/mL with a doubling time of approximately 24 hours were achieved when grown at 28'C with a 24 hour light cycle in sea water and artificial salt water media. Not only did cyanobacteria evolve long before their distant enteric cousins, but they harness nearly all of their energy through photosynthesis. The photosystem is constantly subjected to photo-oxidative damage and degradation. Interesting insight may be gained by studying this complex repair process in the bacterial counterpart to plants, prior to applying these concepts to higher order plant species. Chaperones have been implicated in this repair process. In order to better characterize the stress response of WH8109, I have also isolated the Synechococcus homologue of GroEL using anion exchange and gel filtration chromatography and sucrose gradient centrifugation. The expression levels of this chaperone were analyzed under normal and stress conditions and they have been shown to respond to heat shock and infection.
by Erika M. Erickson.
M.Eng.

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de, la Haba Fonteboa Carlos. "Effects of oxidative stress on plasma membrane fluidity: biological consequences." Doctoral thesis, Universitat Autònoma de Barcelona, 2015. http://hdl.handle.net/10803/311421.

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El estrés oxidativo (OS) es característico de muchas enfermedades y se produce cuando hay un desequilibrio entre oxidantes y antioxidantes, lo cual favorece un estado oxidativo que genera especies reactivas de oxígeno y de nitrógeno. Los lípidos de la membrana plasmática son dianas preferentes del OS y ello tiene como consecuencia la peroxidación lipídica. Este proceso modifica propiedades de la membrana tales como su fluidez, característica física muy importante conocida por modular la localización de las proteínas de membrana y las uniones receptor-ligando. Objetivos: 1) Evaluar el efecto del OS en la regionalización de la fluidez en la membrana plasmática de células vivas tales como macrófagos THP-1 y linfocitos MEC-1, de manera individualizada. 2) Analizar, en estas células, la relación entre la peroxidación lipídica y la fluidez de membrana. 3) Estudiar el efecto del OS sobre la unión receptor-ligando y sobre la fluidez de membrana: lipopolisacárido/receptores de tipo Toll (TLR2/4) en macrófagos y progesterone-induced blocking factor (PIBF)/PIBF-receptor en linfocitos. Material y Métodos: Se estandarizó la metodología two-photon microscopy por primera vez en la Universidad Autónoma de Barcelona, para analizar la fluidez de membrana en células vivas individuales. Conjuntamente se ha desarrollado un nuevo software capaz de medir el tamaño y el número de los dominios lipídicos de membrana. El OS se indujo mediante H2O2 y se empleó la sonda fluorescente Laurdan para detectar las diferencias de fluidez en la membrana plasmática. Se utilizaron LPS y PIBF soluble en macrófagos y linfocitos respectivamente, para analizar interacciones receptor-ligando en condiciones OS. Resultados: En los macrófagos se observó un aumento significativo, dependiente de la concentración de H2O2, en la frecuencia de regiones lipídicas rígidas principalmente compuestas por dominios lipid raft, a expensas de las regiones de fluidez intermedia. Asimismo, se detectó en condiciones de OS, un mayor número, aunque no un mayor tamaño, de dominios lipid raft. La activación de macrófagos con LPS incrementó la frecuencia de regiones fluidas en las membranas, efecto que fue inhibido en condiciones de OS. En cuanto a la función de los macrófagos, se detectó una disminución en la secreción de TNFα en condiciones oxidantes. En los linfocitos se observó un aumentó significativo en la frecuencia de regiones lipídicas rígidas, a expensas de las regiones fluidas, en condiciones de OS. Por otro lado, la unión del PIBF a su receptor, provocó un aumentó en la rigidez de la membrana plasmática debido al clustering de dominios lipid raft. Por el contrario, cuando se indujo OS en linfocitos en presencia de PIBF, se inhibió el clustering de dominios lipid raft y también disminuyó el reconocimiento del receptor de PIBF a su ligando. Conclusiones: 1) Se ha evaluado en células vivas, de forma individual, la dinámica lipídica de la membrana plasmática. 2) Una consecuencia general importante es que, durante el OS, tanto en macrófagos como en linfocitos la membrana plasmática se vuelve más rígida. 3) La fluidez de membrana cambia de forma distinta en los dos tipos celulares estudiados, como consecuencia de las interacciones receptor-ligando: durante la unión LPS-TLR2/4 se observó un aumento en la fluidez de la membrana plasmática de los macrófagos y, por el contrario, durante la unión PIBF/PIBF-R la membrana de los linfocitos se rigidificó, aumentando el clustering de los dominios lipid raft. 4) No obstante, en ambos casos el OS inhibió los cambios en la fluidez de membrana inducidos por la unión receptor-ligando.
Oxidative stress is present in many diseases and it is produced in cells when an imbalance between oxidants and antioxidants occurs, favoring an oxidant status which produce reactive oxygen and nitrogen species. Lipids in plasma membrane are one of the preferential targets giving rise to lipid peroxidation. This process modifies membrane properties such as membrane fluidity, a very important physical feature known to modulate membrane protein localization and receptor-ligand binding. Aims: 1) To evaluate the effect of oxidative stress on plasma membrane fluidity regionalization of single living THP-1 macrophages and MEC-1 lymphocytes. 2) To analyze, in these cells, the relationship between lipid peroxidation and membrane fluidity. 3) To study the effect of oxidative stress on receptor-ligand binding and membrane fluidity: lipopolysaccharide/toll-like receptors (TLR2/4) in macrophages and progesterone-induced blocking factor (PIBF)/PIBF-receptor in lymphocytes. Material and Methods: Two-photon microscopy was standardized for the first time in Universidad Autónoma de Barcelona by our laboratory, to analyze membrane fluidity in single living cells. It was also developed a new software application to analyze membrane lipid domain size and number. Cellular oxidative stress was induced by H2O2; the fluorescent probe Laurdan was applied to evaluate plasma membrane fluidity changes. LPS in macrophages or soluble PIBF in lymphocytes were used to analyze receptor-ligand interactions under oxidative stress. Results: Macrophages showed a significant H2O2 concentration dependent increase in the frequency of rigid lipid regions, mainly attributable to lipid rafts, at the expense of the intermediate fluidity regions. Under oxidative stress conditions, an increase in number, but not in size, of lipid raft domains was detected. Macrophage activation by LPS increase the frequency of fluid regions, which was inhibited by oxidative stress. Concerning macrophage function, secretion of TNFα under oxidative conditions was decreased. Lymphocytes showed a significant increase in the frequency of rigid lipid regions, at the expense of fluid regions, under oxidative stress conditions. Upon PIBF binding to its receptor, lymphocyte plasma membrane became more rigid due to clustering of lipid rafts. However, when PIBF bound lymphocytes were placed in oxidizing conditions, lipid raft clustering was inhibited and PIBF binding to its receptor was also decreased. Conclusions: 1) In single living cells plasma membrane lipid dynamics was evaluated. 2) An important general consequence of oxidative stress is that both in macrophages and lymphocytes plasma membrane becomes more rigid. 3) Receptor-ligand interactions have an effect on membrane fluidity, which vary greatly between the two cell types studied: macrophages and lymphocytes. Upon receptor-ligand binding, macrophage plasma membrane became more fluid while lymphocytes plasma membrane became more rigid. Our results suggest that lipid raft clustering is linked to cell function: upon PIBF binding to its receptor lipid raft clustering occurs in lymphocytes; however, upon LPS/TLR2/4 lipid raft clustering does not occur in macrophages. 4) Nevertheless, the effect induced by receptor-ligand binding on membrane fluidity was inhibited during oxidative stress in both cases.

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O'Keeffe, Stephen George. "The mechanics of growth and residual stress in biological cylinders." Thesis, University of Oxford, 2015. http://ora.ox.ac.uk/objects/uuid:493473f6-b952-4ce3-a2e5-1a79e97afb7f.

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Biological tissue differs from other materials in many ways. Perhaps the most crucial difference is its ability to grow. Growth processes may give rise to stresses that exist in a body in the absence of applied loads and these are known as residual stresses. Residual stress is present in many biological systems and can have important consequences on the mechanical response of a body. Mathematical models of biological structures must therefore be able to capture accurately the effects of differential growth and residual stress, since greater understanding of the roles of these phenomena may have applications in many fields. In addition to residual stresses, biological structures often have a complex morphology. The theory of 3-D elasticity is analytically tractable in modelling mechanical properties in simple geometries such as a cylinder. On the other hand, rod theory is well-suited for geometrically-complex deformations, but is unable to account for residual stress. In this thesis, we aim to develop a map between the two frameworks. Firstly, we use 3-D elasticity to determine effective mechanical properties of a growing cylinder and map them into an effective rod. Secondly, we consider a growing filament embedded in an elastic foundation. Here, we estimate the degree of transverse reinforcement the foundation confers on the filament in terms of its material properties. Finally, to gain a greater understanding of the role of residual stress in biological structures, we consider a case study: the chameleon's tongue. In particular we consider the role of residual stress and anisotropy in aiding the rapid projection of the tongue during prey capture. We construct a mechanical model of the tongue and use it to investigate a proposed mechanism of projection by means of an energy balance argument.

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Davis, Nick K. (Nicholas K. ). "Epitranscriptomics : translational regulation of metabolism, drug resistance and proteostasis during cellular stress." Thesis, Massachusetts Institute of Technology, 2019. https://hdl.handle.net/1721.1/128394.

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This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.
Thesis: Sc. D., Massachusetts Institute of Technology, Department of Biological Engineering, 2019
Cataloged from student-submitted PDF version of thesis.
Includes bibliographical references.
The epitranscriptome -- the naturally occurring system of chemical modifications on ribonucleic acid (RNA) --
is an emerging frontier of research into how changes in the cellular environment are coupled with global rates of protein synthesis. Here we report the development of new analytical and computational approaches to study mechanisms of epitranscriptomic regulation and function in the context of (1) phenotypic antibiotic resistance in bacteria, and (2) proteostasis in eukaryotes. While at least 11 major classes of RNA have been identified to date, this work focuses on transfer RNA (tRNA), the most diversely modified species of RNA that plays a central role in the initiation, elongation and termination of translation. To provide context for investigating the epitranscriptomic regulation of microbial adaptation, we first use multivariate statistical modelling to integrate time-resolved, systems-level analyses of mycobacterial persistence using an in vitro model of tuberculosis infection.
Combining biochemical characterization of cellular pH and redox state, metabolic phenotyping, time-course metabolomics, whole-genome transcriptomics, and quantitative proteomics, we demonstrate that starved Mycobacterium bovis BCG (BCG) adapts to starvation by entering a ketotic state that results from coordinated metabolic shifts towards lipolysis and fatty acid [beta]-oxidation. We also show that management of toxic ketone body intermediates appears to be mediated by cytochrome P450 (CYP)-linked ketolysis and carbon cycling through CO₂ fixation, as evidenced by elevated endogenous reactive oxygen species production during starvation and the sensitivity of starved persisters to well-known CYP poisons. Using this model of mycobacterial pathogenesis, we next describe how BCG responds to nutrient deprivation by reprogramming the tRNA epitranscriptome to mediate selective translation of codon-biased stress response genes.
We discuss how insights from preliminary experiments with a new in-house method, Absolute QUAntification RNA-Seq (AQUA RNA-Seq), will deepen our mechanistic understanding of this alternative genetic code, and also describe a strategy for chemotherapeutic intervention to reverse phenotypic drug resistance. Finally, we detail the development of a new high-throughput platform to identify and quantify the role of the epitranscriptome in translational fidelity in Saccharomyces cerevisiae. Our results indicate that loss of certain tRNA-modifying enzymes induces the aggregation of stress response proteins with amino acid misincorporations that map to specific codon sites.
The research conducted under this thesis (1) advances our fundamental understanding of how genes are regulated at the level of translation, (2) establishes the role of the epitranscriptome in regulating cellular adaptation to physiological stringency, and (3) provides mechanistic insights into how the epitranscriptome can be engineered for the development of new RNA-targeted medicines.
by Nick K. Davis.
Sc. D.
Sc.D. Massachusetts Institute of Technology, Department of Biological Engineering

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Kalkeren, Antje Afien van. "Stress-induced decrease of intestinal barrier functioning: a general biological phenomenon?" [S.l. : Amsterdam : s.n.] ; Universiteit van Amsterdam [Host], 2002. http://dare.uva.nl/document/65661.

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Parsons, Harriet T. "Transport and metabolism of symplastic and apoplastic ascorbate during oxidative stress." Thesis, University of Edinburgh, 2009. http://hdl.handle.net/1842/3075.

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Reactive oxygen species (ROS) are produced continuously in plants and act as important signalling molecules in many cellular processes including stress and defence responses. ROS can arise from external sources as well as being generated by the plant. Pollutants, such as ozone, enter the leaf via stomata and dissolve in the apoplast. ROS can arise both intracellularly and apoplastically: superoxide is produced during photosynthesis as well as by the plasma membrane bound NADPH oxidase during the oxidative burst. Under abiotic stresses such as drought or high light-intensity, superoxide production from photosynthetic electron flow is increased. Ascorbate plays a crucial role in symplastic and apoplastic ROS metabolism. Intracellular ascorbate metabolism is highly regulated; it is coupled to glutathione oxidation and reduction and is under tight enzymic control. Export of ascorbate into the apoplast increases during ozoneinduced stress. The apoplast redox state is considered to be more variable than the symplasm. Ascorbate is thought to be taken up from the apoplast in its oxidised form, DHA, via specific carriers, implying tight regulation of apoplastic/symplastic ascorbate transport. An apoplastic ascorbate breakdown pathway has recently been described by Green and Fry (2005). Ascorbate is oxidised and hydrolysed to yield oxalate via two novel intermediates, cyclic oxalyl L-threonate (cyc.ox.thr.) and 4-O-oxalyl-L-threonate (ox.thr.) A novel esterase is thought to catalyse the hydrolysis of ox.thr. to oxalate. Dehydro-L-ascorbate DHA was also hydrolysed to L-2,3-diketogulonate (DKG) which broke down to two unidentified compounds, C and E. It was not known whether this pathway operated intracellularly and how increased ROS production might affect flux through this pathway. The pathway, described, in the culture medium of 5-day-old rose cell suspension cultures but had not been investigated in planta. Intracellular and extracellular metabolism of [14C]ascorbate in [14C]ascorbate-loaded cells was investigated in response to oxidative stress induced by 0.1 and 1 mM H2O2 and 1 and 10 μM methyl viologen (MV2+). The symplasm became more oxidised in response to 0.1 mM H2O2; DHA levels increased and ascorbate decreased, but ox.thr. and oxalate, products of irreversible ascorbate breakdown, did not accumulate. Symplastic ox.thr. and oxalate accumulated in response to MV2+ and 1 mM H2O2. Ox.thr. and oxalate were observed in-planta. Flux through the pathway was increased in transgenic tobacco plants which overexpressed the cell wall-located enzyme ascorbate oxidase, suggesting that the redox state of the apoplast could increase apoplastic ascorbate breakdown via ox.thr. The rate of production of oxalate in vivo compared to in vitro studies suggested that the esterase was located to the symplasm as well as the apoplast. Oxalate did not appear to be metabolised further. Compounds C and E were neither observed in planta nor in 10-day old rose cell cultures. DKG and cyc.ox.thr. were present only in low levels. Export of 14C in [14C]ascorbate loaded cells increased in response to 1 and 5 mM H2O2. Increased export was characterised by a rapid response during the first 2 min of H2O2 exposure. In Arabidopsis and rose cell suspension cultures, export was often observed to occur in series of pulses. The amplitude of pulses increased within the first 2 min of H2O2 exposure. This was not thought to be a result of membrane disruption. 14C appeared to be exported as [14C]ascorbate and taken up as [14C]DHA, with minimal oxidation in the culture medium. These results provide more insight into intracellular ascorbate breakdown via ox.thr. and suggest that oxalate could accumulate in response to oxidative stress in plants. The export of ascorbate/DHA in pulses in response to H2O2 hints at novel mechanisms of regulation of ascorbate/DHA transport across the plasma membrane.

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12

Bibbey, Adam. "Constitutional and behavioural correlates of individual differences in biological stress reactivity." Thesis, University of Birmingham, 2015. http://etheses.bham.ac.uk//id/eprint/5736/.

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This thesis examined potential corollaries of individual differences in cardiovascular and/or cortisol reactions to acute psychological stress, with specific focus upon personality and behavioural characteristics. Chapter 2 reported that a negative constellation of the Big 5 personality traits, higher neuroticism and lower openness and agreeableness, was associated with blunted physiological reactivity. Chapter 3 demonstrated that, in comparison to individuals without Type D personality, Type Ds had greater physiological reactivity during social stress, but lower reactivity when exposed to largely asocial stress. Both these studies also reported dissociation between subjective and physiological stress responses. Chapter 4 reported that individuals with problematic Internet use and/or excessive alcohol consumption did not differ in physiological stress reactivity in comparison to non-dependent controls. Finally, Chapter 5 demonstrated that, compared to exaggerated cardiovascular stress responders, blunted reactors had greater levels of behavioural impulsivity. Overall, the research reported provides evidence that there is dissociation between affective and physiological stress responses, the context in which the stressful situation is experienced is important, and finally, blunted reactivity appears to be related to adverse outcomes which are stable rather than transient, suggesting that it may be a peripheral marker of dysfunction in the brain systems that support motivated behaviour.

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13

Newell, Tracey. "Neurocognition in Post-Traumatic Stress Disorder." Thesis, University of Southampton, 2009. https://eprints.soton.ac.uk/162759/.

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The negative behavioural and emotional symptoms of Post-Traumatic Stress Disorder (PTSD) have been extensively reported in the literature. However, much less is known about the neuropsychological and neurobiological characteristics of the disorder. This thesis consists of two papers, the first being a review which highlights the emerging picture of literature in the field of neuropsychology in PTSD, with particular reference to findings in those cognitive domains of general intellectual functioning, memory, attention and executive function. Given that the findings associated within these domains are mixed, the second paper reports the outcome from a neuropsychological study of cognitive differences that was conducted to contribute to current knowledge in the area of neurocognition and visual memory in PTSD in particular. Trauma exposure, current PTSD, depressive and anxiety symptoms and performance on a range of neuropsychological tests were examined in tertiary care outpatients with PTSD (n=26), individuals who had been exposed to severe trauma but without current PTSD (n=26), and healthy controls (n=26). In addition to previously reported deficits in verbal learning and fluency in PTSD, deficits in visual spatial memory were also found. These observable deficits in visual memory may reflect characteristic features of PTSD, such as reported difficulties in remembering certain aspects of traumatic events and the presence of visual flashbacks. It is uncertain whether these deficits represent a risk factor for PTSD, or a consequence of trauma, as suggested by research in animal models.

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14

Sheen, Tamsin, and n/a. "Osmotic and desiccation stress-tolerance of Serratia entomophila." University of Otago. Department of Microbiology & Immunology, 2008. http://adt.otago.ac.nz./public/adt-NZDU20081208.114925.

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Serratia entomophila, the causative agent of amber disease, is an endemic bacterium used for the biocontrol of New Zealand grass grub larvae. Although the available biopesticide is effective, its use is limited to areas where sub-surface application is feasible, and is also impacted by soil conditions such as moisture levels and osmolarity. The aim of this study was to elucidate the responses of S. entomophila to osmotic and desiccation stresses in relation to challenges encountered during production, storage and soil application, with the goal of developing a more robust and versatile biocontrol agent. RpoS is a key factor in the stress response of many enteric bacteria. In order to dissociate the effect of RpoS from subsequent cellular stress studies, an rpoS mutant was constructed by site-directed mutagenesis. Assessment of the rpoS mutant showed that RpoS was not implicated in NaC1 or desiccation tolerance of S. entomophila. The rpoS mutant was instead found to have enhanced salt tolerance and could be distinguished from the wild-type by the ability to ferment arabinose, a phenotype that was confirmed through complementation. Complete abolition of the amber disease process was observed using an rpoS strain also missing the Sep virulence genes, suggesting that RpoS is a regulator of the S. entomophila anti-feeding prophage (Afp). These findings indicate a subtle interplay between NaC1 tolerance, virulence and RpoS-mediated regulation of amber disease in S. entomophila. A transposon mutagenesis screen was carried out to identify genes associated with NaC1 tolerance in S. entomophila. Fourteen mutants displaying NaC1 sensitivity were identified, two of which had mutations in genes with potential implications for the formulation of the bacterium as a biocontrol agent. The gene leuO that encodes a LysR-family transcriptional regulator was found to be essential for S. entomophila NaC1 tolerance. The toxicity of increased cellular LeuO from an over-expression vector led to the investigation of the effects of leuO mutation on the proteome. Multiple protein changes observed by two-dimensional gel analysis suggested that LeuO may be a global regulator in S. entomophila, as has been hypothesised for Salmonella species. A second NaC1-sensitive mutant contained an insertion in afp15, the product of which is thought to be involved in assembly of the Afp. As well as being sensitive to NaC1, the afp15 mutant was unable to induce the anti-feeding component of amber disease, again highlighting the link between stress tolerance and virulence in S. entomophila. This study also determined that pre-exposure to NaC1 in conjunction with the provision of exogenous glycine betaine significantly enhanced the survival of S. entomophila either in a desiccated state or after application to soil, regardless of the soil moisture content. The implication of this finding on the future formulation of S. entomophila led to investigation of the underlying genetic mechanisms involved in glycine betaine synthesis and NaC1 tolerance. The genes involved in glycine betaine biosynthesis from choline were identified through genomic comparison, degenerate PCR and primer walking. A 6.5 kb region was sequenced and found to contain four genes with homology and similar chromosomal arrangement to the E. coli bet genes (betTIBA). The S. entomophila betIBA genes comprised an operon, flanked by the divergently-transcribed betT gene whose product is responsible for choline transport. To ascertain the relative transcription levels of components of the bet operon, quantitative RT-PCR was performed. Results of qRT-PCR showed that choline in conjunction with NaC1 induced the greatest levels of bet gene transcription, and that levels of the betA transcript were significantly lower than those of the other bet genes. Examination of the betA 5� non-coding region identified a previously undetected hairpin region, possibly accounting for the observed decrease in betA transcript levels. The findings of this study have significantly advanced our understanding of how S. entomophiia responds to stress, and will contribute to the development of formulation strategies for the production of a robust product capable of application to pasture by a range of teclmiques. In addition, there is significant potential to utilise these findings in the development of other bacterial inocula for a range of biotechnological applications.

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15

Lucas, Robyn Marjorie, and robyn lucas@anu edu au. "Socioeconomic status and health: exploring biological pathways." The Australian National University. National Centre for Epidemiology and Population Health, 2004. http://thesis.anu.edu.au./public/adt-ANU20060426.095241.

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The cross-sectional Biomarkers Study was undertaken in Canberra, Australia (2000-2002) to examine the role of psychosocial factors in the socioeconomic health gradient, via physiological changes consequent upon activation of the neuroendocrine stress response.¶ The study population was derived from healthy 40-44 year old men and women already participating in a longitudinal cohort study. Using data from the cohort study, four groups with similar occupational status were formed. The study sample was randomly selected within these groups, thus representing the socioeconomic spectrum.¶ A pilot study involved 60 participants with blood and saliva samples measured on two occasions. A further 302 people had blood and saliva samples taken on one occasion. Socioeconomic status was measured by occupational code and status, personal and household income, education and perceived position in the community and in Australia. Psychosocial and behavioural factors, including job strain, job security, coping style, anxiety, depression, optimism, self-esteem, sense of belonging and trust, social support, smoking, exercise and alcohol intake were assessed by selfreport. Five biological parameters: plasma fibrinogen, glycated haemoglobin, waisthip ratio, serum neopterin and salivary IgA were measured as outcome variables.Three hypotheses were tested:¶ 1. There is a socioeconomic gradient in measures of psychosocial stress, and of psychological resilience.¶ 2. There is a socioeconomic gradient in biological measures that have a plausible¶ association with future disease. 3. Psychosocial factors mediate the demonstrated association between socioeconomic status and the biological measures.¶ Data analysis confirmed a socioeconomic gradient in some psychosocial and behavioural variables: economic strain (r=-0.44, p<0.001), job demands (r=0.45, p<0.001), job control (r=0.26, p<0.001), active coping style (r=0.28, p <0.001), sense of optimism (r=0.24, p<0.001), social capital (r=0.26, p<0.001), job security (r=0.17, p=0.002), job marketability (r=-0.16, p=0.005), sense of belonging (r=0.22, p<0.001), number of adverse life events (r=-0.13, p=0.01) and positive interaction with family and friends (r=0.20, p<0.001 ), vigorous physical activity (r=-0.16, p=0.002), alcohol consumption (r=0.30, p<0.001) and smoking status (r=-0.25, p<0.001). There was no socioeconomic gradient in anxiety, depression, neuroticism, hostility, locus of control, self-esteem, perceived stress or mental health (SF-12). Four of the five biological markers varied with socioeconomic status: plasma fibrinogen (female (F): r=-0.26, p=0.002, male (M) r=-0.08, p=0.30), glycated haemoglobin (F: r=-0.23, p=0.01, M: r=-0.11, p=0.17), waist-hip ratio (F: r=-0.19, p=0.03, M: r=-0.27, p<0.001), serum neopterin (F: r=-0.21, p=0.009, M: r=-0.04, p=0.56), salivary IgA (F: r=-0.07, p=0.38, M: r=0.004, p=0.97). A more adverse biological profile was associated with lower socioeconomic status. Work characteristics, coping style, smoking and exercise were particularly important mediators of the association between the biological markers and socioeconomic status. Particular psychosocial factors were consistent mediators of the association between specific biomarkers and socioeconomic status (with little variation for different measures of socioeconomic status). However, the particular psychosocial factors providing significant mediation varied for the different markers.¶ In this sample of healthy 40-44 year olds, four out of five biological markers showed moderate socioeconomic variation with a more favourable profile associated with higher SES. The data provide limited support for the importance of psychosocial factors in the socioeconomic health gradient.

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16

Hofer, Tim. "Method development for analysis of 8-oxodG as a biomarker for oxidative stress /." Stockholm : Karolinska Univ. Press, 2001. http://diss.kib.ki.se/2001/91-7349-064-4/.

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17

Bur, H. (Hamid). "Biological prognostic and predictive markers in Hodgkin lymphoma." Doctoral thesis, Oulun yliopisto, 2018. http://urn.fi/urn:isbn:9789526219455.

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Abstract Hodgkin lymphoma (HL) is among a heterogeneous group of lymphomas. Over 80% of all patients can be cured with chemo- and radiotherapy. HL has become a model to study long-term effects of radio- and chemotherapy, because of the excellent prognosis. There are a significant number of patients who suffer or die because of the treatment-related long-term toxicity. The aim of this work was to discover new possible biological factors to predict poor prognosis and offer new aspects to individualize patient treatment in a convenient manner in HL. The retrospective study involved HL patients uniformly treated in 1997–2015. Immunohistochemistry was used to determine the expression of various biological markers, including oxidative stress markers 8-hydroxydeoxyguanosine (8-OHdG) and nitrotyrosine and the antioxidant enzymes manganese superoxide dismutase (MnSOD) as well as peroxiredoxins (Prx II, Prx III, Prx V, Prx VI) in HL patient samples. Using immunohistochemistry, we also evaluated expression of hypoxia-inducible factors (HIF-1α, HIF-2α), prolyl hydroxylase domain enzymes (PHD1, PHD2, PHD3), the epigenetic regulator lysine (K)-specific demethylase 4 (KDM4A, KDM4B, KDM4D) as well as sirtuins (SIRT1, SIRT4, SIRT6), the DNA-repair proteins Human Rap1 interacting factor 1 (Rif1) and O6-alkylguanine DNA alkyltransferase (MGMT) from representative classical Hodgkin lymphoma (cHL) patient samples. Low-level expression of 8-OHdG was associated with poorer relapse-free survival (RFS) in advanced-stage HL and a high extent of MnSOD predicted early relapse in the whole HL cohort. Strong expression of PHD1, KDM4B and KDM4D predicted dismal RFS in radiotherapy-treated cHL patients. The results also showed that strong expression of HIF-1α, SIRT6 and Rif1, and SIRT6 together with Rif1, were associated with prolonged RFS, especially in advanced-stage radiotherapy-treated cHL patients. In multivariate analysis, PHD1, MnSOD, 8-OHdG and Rif1 separately and together with SIRT6 were statistically significant predictors of RFS. The results reflect the significance of the studied biomarkers in HL, especially in radiotherapy-treated patients. This might be beneficial when individualizing treatment strategies, avoiding overtreatment and controlling long-term treatment-related toxicity. Further research, however, is needed to confirm these preliminary findings
Tiivistelmä Hodgkinin lymfooma (engl. HL) kuuluu heterogeeniseen imukudossyöpien eli lymfoomen ryhmään. Yli 80 % lymfoomapotilaista voidaan parantaa solunsalpaaja- ja sädehoidon avulla. Hyvän ennusteen takia HL- tutkimuksen tärkeä painopiste on säde- ja solunsalpaajahoidon pitkän ajan haittavaikutukset. Huomattava määrä potilaista kärsii tai jopa kuolee hoitoon liittyvistä pitkäaikaishaitoista johtuen. Tämän tutkimuksen tarkoituksena oli löytää uusia mahdollisia biologisia tekijöitä, jotka ennakoisivat taudin huonoa ennustetta ja samalla antaa uusia näkökulmia HL potilaiden hoidon yksilöllistämiseen. Tämä retrospektiivinen tutkimus käsitti vuosina 1997-2015 samanlaisesti hoidettuja Hodgkinin lymfooma -potilaita. Immunohistokemiallisilla värjäyksillä määritettiin biologisten merkkiaineiden, mukaan lukien oksidatiivisen stressin markkereiden 8- hydroksideoksiguanosiinin (8-OHdG) ja nitrotyrosiinin, sekä antioksidanttientsyymien mangaanisuperoksidi-dismutaasin (MnSOD) sekä peroksiredoksiinien (Prx II, Prx III, Prx V, Prx VI) ilmentymistä HL -potilasnäytteissä. Määrittelimme myös immunohistokemiallisilla värjäyksillä epigeneettisten säätelijöiden lysiinin spesifisen demetylaasientsyymin 4 (KDM4A, KDM4B, KDM4D) sekä sirtuiinien (SIRT1, SIRT4, SIRT6), hypoksiaa indusoivien tekijöiden (HIF-1α, HIF-2α), prolyylihydroksylaasientsyymien (PHD1, PHD2, PHD3) ja DNA:ta korjaavien proteiinien Rap1 vaikuttuvan tekijä 1 (Rif1) ja O6-metyyliguaniini-DNA metyylitransferaasin (MGMT) ilmentymistä edustavissa klassista Hodgkinin lymfoomaa sairastavien potilaiden (engl. cHL) näytteissä. Heikko 8-OHdG värjäytyminen ennusti ennenaikaista taudin uusiutumaa levinneessä HL:ssa ja korkea MnSOD ilmaantuvuus ennusti ennenaikaista taudin uusiutumaa koko HL -ryhmässä. Sädehoidetuilla cHL potilailla voimakas PHD1, KDM4B ja KDM4D värjäytyminen ennusti ennenaikaista taudin uusiutumaa. Tulokset osoittivat myös, että erityisesti sädehoidetuilla levinneen taudin cHL potilailla voimakas HIF-1α, SIRT6, Rif1 ja SIRT6 yhdessä Rif1:n kanssa oli yhteydessä pidentyneeseen uusiutumavapaaseen aikaan. Monimuuttuja-analyysissä PHD1, MnSOD, 8-OHdG ja Rif1 itsenäisenä ja yhdessä SIRT6 kanssa ennustivat tilastollisesti merkitsevästi taudin ennenaikaista uusiutumaa. Tulokset osoittavat näiden eri biomarkkereiden merkittävyyden HL:ssä, erityisesti sädehoitoa saaneilla potilailla. Tuloksista voi olla hyötyä, kun hoitokäytäntöjä yksilöidään, mikä voisi helpottaa välttämään liiallista hoitoa ja hallitsemaan pitkäaikaisiin hoitoihin liittyviä haittoja. Näiden alustavien havaintojen vahvistamiseksi tarvitaan kuitenkin lisätutkimuksia

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18

Dovey, Terence Michael. "Stress-induced feeding : biological, psychological and individual mechansims that promote over-consumption." Thesis, University of Liverpool, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.433727.

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19

Giesen, Myra Jayne. "Late prehistoric populations in the Ohio area : biological affinities and stress indicators /." Connect to resource, 1992. http://rave.ohiolink.edu/etdc/view.cgi?acc%5Fnum=osu1244660788.

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20

Henry, Michelle. "The impact of psychosocial stress and biological sex on false recognition memory." Master's thesis, University of Cape Town, 2010. http://hdl.handle.net/11427/14332.

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Includes bibliographical references (leaves 96-114).
Based on the premise that both the hippocampus and pre-frontal cortex are affected by cortisol and involved in declarative memory processes, the current research aimed to confirm that psychosocial stress can lead to increased rates of false recognition memory errors in humans. In addition, it attempted to show that false recognition error rates differ depending on biological sex and the original stimulus type, thus extending and validating the research done by Gallo and colleagues (2004) on material specificity in false memory. Participants in a Stress group (15 males and 13 females) were exposed to a procedure designed to induce mild psychosocial stress, whereas participants in a Relax group (15 males and 14 females) were exposed to a period of relaxation. Salivary cortisol, heart rate, and subjective self-report measures were used to determine participants' stress levels. All participants completed a false memory task, entailing 3 different recognition tests, on 2 consecutive days. Results showed that under both stressful and non-stressful conditions, pictures were better remembered than words, and that this effect was not mediated by biological sex. However, false recognition errors were greater for pictures compared to words, and neither experimental condition nor biological sex mediated this effect. It was also found that the amount of false memory recognition errors made was not affected by the presence of a stressor, as participants in the Stress and Relax groups performed equally. This result is in contrast with previous studies which indicate that false memories increase under stressful conditions. Furthermore, the impact of stress on false memory was not mediated by biological sex, as both male and female participants in the Stress group performed equally. False memory rates increased over a 24- hour retention period in all participants - however the decay of true memory yielded inconsistent results. This was the first study to examine the material specificity of false memory under stressful conditions. It was also the first study to examine whether the amount of false memory errors made under stressful conditions differed between male and female participants. Therefore, the question of whether the material specificity of false memory is affected under stressful conditions and mediated by biological sex remains open for further research. The use of varying false memory paradigms and larger sample populations would help clarify this question.

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Giesen, Myra Jayne. "Late prehistoric populations in the Ohio area: biological affinities and stress indicatiors." The Ohio State University, 1992. http://rave.ohiolink.edu/etdc/view?acc_num=osu1244660788.

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22

Giesen, Myra J. "Late prehistoric populations in the Ohio area : biological affinities and stress indicators /." The Ohio State University, 1992. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487778663284737.

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23

Barber, Vicki S. "Effects of oxidative stress and neuroprotection in apoptosis in neuronal cell models." Thesis, Aston University, 2002. http://publications.aston.ac.uk/10995/.

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The PC12 and SH-SY5Y cell models have been proposed as potentially realistic models to investigate neuronal cell toxicity. The effects of oxidative stress (OS) caused by both H2O2 and A on both cell models were assessed by several methods. Cell toxicity was quantitated by measuring cell viability using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) viability assay, an indicator of the integrity of the electron transfer chain (ETC), and cell morphology by fluorescence and video microscopy, both of which showed OS to cause decreased viability and changes in morphology. Levels of intracellular peroxide production, and changes in glutathione and carbonyl levels were also assessed, which showed OS to cause increases in intracellular peroxide production, glutathione and carbonyl levels. Differentiated SH-SY5y cells were also employed and observed to exhibit the greatest sensitivity to toxicity. The neurotrophic factor, nerve growth factor (NGF) was shown to cause protection against OS. Cells pre-treated with NGF showed higher viability after OS, generally less apoptotic morphology, recorded less apoptotic nucleiods, generally lower levels of intracellular peroxides and changes in gene expression. The neutrophic factor, brain derived growth factor (BDNF) and ascorbic acid (AA) were also investigated. BDNF showed no specific neuroprotection, however the preliminary data does warrant further investigation. AA showed a 'janus face' showing either anti-oxidant action and neuroprotection or pro-oxidant action depending on the situation. Results showed that the toxic effects of compounds such as A and H2O2 are cell type dependent, and that OS alters glutathione metabolism in neuronal cells. Following toxic insult, glutathione levels are depleted to low levels. It is herein suggested that this lowering triggers an adaptive response causing alterations in glutathione metabolism as assessed by evaluation of glutathione mRNA biosynthetic enzyme expression and the subsequent increase in glutathione peroxidase (GPX) levels.

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24

Dahl, Joakim Johnson Richard K. Sandin Leonard. "Detection of human-induced stress in streams : comparison of bioassessment approaches using macroinvertebrates /." Upsala : Swedish University of Agricultural Sciences, 2004. http://diss-epsilon.slu.se/archive/00000708/.

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Thesis (doctoral)--Swedish University of Agricultural Sciences, 2004.
Thesis documentation sheet inserted. Appendix reproduces three papers and manuscripts co-authored with R.K. Johnson and two papers co-authored with R.K. Johnson and L. Sandin. Includes bibliographical references. Also issued electronically via World Wide Web in PDF format; online version lacks appendix.

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25

Løtvedt, Pia Katrine. "Domestication and early experiences in chickens : Behavior, stress and gene expression." Licentiate thesis, Linköpings universitet, Biologi, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-143053.

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A number of animal species have undergone domestication, the process of becoming adapted to living in captivity and in proximity to humans. Common for these species is that they have all developed certain traits, including changes to coat color, body size and level of fearfulness. This has been termed the domestic phenotype. Among these traits is also an attenuation of the response to stress, both behaviorally and physiologically. Thus, release of glucocorticoids such as cortisol or corticosterone is lower in domesticated species. However, the underlying mechanism for this is not yet well understood. In this thesis, we have investigated genetic mechanisms for the attenuation of the physiological stress response in ancestral chickens, the Red Junglefowl, and domesticated chickens, the White Leghorn. We found a number of genes that differed in expression between the two breeds in several tissues involved in the stress response. Among the most interesting findings were lower expression of genes involved in production and secretion of ACTH in the pituitary, and in the production of glucocorticoids in the adrenal glands, in the domesticated White Leghorns. We also found higher expression of the glucocorticoid receptor in White Leghorns, indicating that they may have a more efficient negative feedback of the physiological stress response. We then investigated the transcriptome of the chicken pituitary more closely, and we discovered that a number of genes highly involved in several important physiological axes showed differential expression between the ancestral and the domesticated breed. Among these were genes involved in the stress response, the reproductive system, and in metabolism and growth. As these traits are modified in domesticated species, our results suggest that changes to gene expression in the pituitary may be an important underlying factor of the domestic phenotype. A separate aim of this thesis was to investigate effects of hatching time in chickens on their subsequent phenotype. Time of hatching constitutes an early experience that may differ between individuals, and we therefore hypothesized that differences in hatching time would affect chickens later in life. While a number of studies have been performed on hatching time and post-hatch growth, very little work has been done on effects on behavior. We found that the time of hatching had sex-specific effects. Hatching times in females were negatively correlated with body weight, whereas in males, behaviors such as reaction to novelty and spatial learning were affected. As time of hatching is governed by various hormones, including thyroid hormone and corticosterone, we suggest that changes to the levels of these hormones could affect both hatching time and post-hatch phenotypes. Understanding these mechanisms better would be beneficial in terms of production, where batch homogeneity is important, in research on early experiences and the potential for maternal programming, and in evolutionary questions on trade-off between different life strategies.

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Harvey, Joanna Sarah. "Stress in British Army personnel." Thesis, Liverpool John Moores University, 1999. http://researchonline.ljmu.ac.uk/5987/.

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There is considerable research to date in the field of stress, particularly with respect to questionnaire research. There is, however, a lack of recent research on stress in the British Army which addresses either traumatic or organisational stress. This study considers soldiers' experiences of both occupational and traumatic stress, in addition to identifying the contribution of an individual's expectations and evaluations of a deployment, on mental well-being. Furthermore, this research methodology incorporates standardised psychological questionnaires, free response items and interviews with personnel, which serve to provide a comprehensive approach with high face validity. This study aims to encompass the major aspects which influence the onset and course of stress, including stress experiences, individual differences and coping, in one model. Both studies incorporate traumatic and organisational stress, which is particularly relevant in the military profession, where there is risk of exposure to traumatic events. This study attempts to redress the paucity of research on stress in the British Army as a result of conflicts since WWII, in addition to countering the lack of research into occupational stress in the British Army, or information of a longitudinal nature. This study also provides a much needed 'baseline' of data across the British Army regarding stress experiences and reactions. The study also incorporates qualitative aspects, where the respondents are asked what they define as stressful experiences, as opposed to completing a list of pre-defined 'stressors', in addition to incorporating interviews to validate the responses. Finally, an individual's evaluation of a situation, or belief in their actions is taken into account in this research. It is argued that this is of particular importance in a military operational context, when soldiers are no longer deploying in defence of their country against an external threat. It was therefore considered important to establish if there were any effects on psychological well-being based on an individual's evaluation of the deployment situation. This research was conducted in two phases: Study 1 which is a cross-sectional study, proportionate to size across the British Army, and Study 2 which is a longitudinal survey, before and after a six month operational deployment to Northern Ireland. The questionnaire material incorporates both standardised questionnaires and a specific Army questionnaire designed for the study. Support was found for the proposed models of both general (Study 1) and operational stress (Study 2). Previous findings were supported concerning the interrelationships between neuroticism, anxiety, emotion focused coping and adverse life events, and were independent of mastery, self esteem, problem focused coping and well-being. Thirty three and thirty nine percent of respondents reported General Health Questionnaire (GHQ12) values above the cut off criteria for Study 1 and Study 2, respectively. Individual differences concerning reported mental health were noted, particularly with respect to age, marital status and the occurrence of a significant life event. Recommendations addressed the lack of clear evidence for adopting a 'screening out' procedure based upon personality characteristics for mainstream Army deployments. It was suggested that the traumatic aspects of the research could benefit from an alternative questionnaire to the Impact of Events Scale (IES), due to some of the difficulties found in using the questionnaire. It was also suggested that coping strategies should be investigated in greater detail, within a more context specific manner with tighter response definitions. Finally, it is believed that the impact of cumulative operational deployments on the mental health of soldiers needs to be thoroughly researched.

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Chilufya, Jedaidah, Kousha Mohensi, and Aruna Kilaru. "The Role of Anandamide in Biotic Stress Tolerance in Mosses." Digital Commons @ East Tennessee State University, 2015. https://dc.etsu.edu/etsu-works/4843.

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Mosses are small avascular bryophytes with a haploid dominant gametophyte and a diploid sporophyte stage. The gametophyte cells are single layered and lack a protective cuticle, which is the first line of defense in vascular plants. These factors would render them highly susceptible to stress but on the contrary, mosses have flourished on land for the past 450 million years with tolerance to both abiotic and biotic stress. Occurrence of unique lipids in bryophytes was considered as an adaptive means to survive harsh terrestrial condition. A recent study identified a lipid metabolite, anandamide in the Physcomitrella patens. Anandamide (NAE 20:4) belongs to a group of fatty acid ethanolamides or N –acylethanolamines (NAEs). In eukaryotes, NAEs were shown to play an important role in mediating stress responses. In plants, NAE 14:0 has been implicated in biotic stress response; its levels increased up to 50-fold in elicitor-treated tobacco plants, along with induction of defense gene expression and inhibition of alkalization. In animals anandamide acts as an endocannabinoid ligand and mediates several physiological responses including stress. This study aims to use P. patens as the model system because of its available genomic database and prior studies on biotic stress, to examine if NAE 20:4 contributes to their ability to tolerate biotic stress. It is hypothesized that the occurrence of anandamide will play a role in mediating biotic stress tolerance in P. patens. To test this hypothesis, three specific aims are proposed. They are to determine the effect of 1) elicitor-treatment on NAE and fatty acid profile in the moss, 2) anandamide on elicitor-induced morphological and physiological changes in the moss and 3) anandamide on elicitor-induced defense gene expression in moss. Mosses utilize similar defense mechanisms as flowering plants and disease symptoms can easily be studied using microscopy because of their haploid dominant gametophyte stage with monolayer cells. The induction of defense gene expression will be studied by quantitative PCR and changes in lipid profile by selective lipidomics. This study is expected to provide novel insights into the role of anandamide in early land plants, specifically in response to biotic stress.

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Raczynski, Arkadiusz R. (Arkadiusz Roland). "Citrobacter rodentium induced liver changes in C57BL/6 mice : animal model of acute inflammatory stress and injury." Thesis, Massachusetts Institute of Technology, 2011. http://hdl.handle.net/1721.1/67208.

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Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biological Engineering, 2011.
Each page number preceded by chapter or appendix number. Cataloged from PDF version of thesis.
Includes bibliographical references (p. F-150 - F-163).
The activation of inflammatory responses, while critical for host defense, contributes to hepatic injury in numerous acute and chronic liver disease states as well as drug-induced liver injury (DILI). The interactions that mediate susceptibility to liver injury and disease, however, are still poorly understood, underscored by the complexity of immune interactions and the diverse cellular composition and functions of the liver. Using Citrobacter rodentium, a well characterized rodent-specific enteric pathogen as a source of extrahepatic inflammatory stress; host liver responses, metabolic dysregulation, and susceptibility to injury in C57BL/6 mice were investigated. For the first time, we show altered liver pathology during the early course of C. rodentium infection, characterized by periportal necrosis indicative of thrombic ischemic injury, correlating with distinct circulating and tissue specific cytokine/chemokine profiles. Using Acetaminophen (APAP), a widely used analgesic and well-characterized hepatotoxin, we evaluated liver responses in isolation and in the context of host inflammation to gain insight into the role of live bacterial infection in altering liver metabolism and susceptibility to DILI. We combined systemic and tissue-specific cytokine/chemokine levels, clinical serum chemistries, and histopathological assessments of hepatic and enteric inflammation and necrosis to measure molecularlevel responses to treatment and their physiological effect. Using principal components analysis (PCA), clustering, partial least squares regression (PLSR), and a combination mutual-information-correlation network, enabled detection and visualization of both linear and nonlinear dependencies between molecules and physiological states across tissues and timepoints. C. rodentium-induced inflammatory stress was finally investigated for its potential in altering drug pharmacokinetics (PK) of substrates varying in their metabolic biotransformation and clearance mechanisms. Infection resulted in increased systemic oral exposure (AUC) of clinically relevant xenobiotics such as verapamil, propranolol, and digoxin. Functionally, these changes were not found dependent on CYP-mediated biotransformation of parent compounds; rather, they appear driven more by proposed gut barrier compromise. In conclusion, gastrointestinal infection with C. rodentium alters systemic and hepatocytes specific responses, not previously appreciated from this enteric pathogen, making it a useful model for studying host-pathogen interactions under acute hepatic inflammatory stress and injury.
by Arkadiusz R. Raczynski.
Ph.D.

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Lucas, Robyn Marjorie. "Socioeconomic status and health : exploring biological pathways /." View thesis entry in Australian Digital Theses, 2003. http://thesis.anu.edu.au/public/adt-ANU20060426.095241/index.html.

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30

Larussa, Thomas K. (Thomas Keith). "Anxiety, Locus of Control and Stress in Adoptive and Biological Parents of Adolescents." Thesis, University of North Texas, 1995. https://digital.library.unt.edu/ark:/67531/metadc278428/.

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31

Austin, Kimberley W. "Biological Mechanisms and Symptom Outcomes of Uncertainty and Psychological Stress in Parkinson’s Disease." VCU Scholars Compass, 2017. http://scholarscompass.vcu.edu/etd/4716.

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The purpose of this work was to examine biological mechanisms and symptom outcomes of illness uncertainty and psychological stress in Parkinson’s disease (PD). Parkinson’s disease is a chronic, progressive neurodegenerative disorder characterized by complex symptoms that fluctuate in onset, severity, level of disability, and responsiveness to treatment. In addition to characteristic motor symptoms of tremor, rigidity, bradykinesia, and postural instability, a considerable number of individuals with PD also experience debilitating pain, fatigue, and medication-induced motor complications of dyskinesia, dystonia, and on-off phenomena. The unpredictable nature of PD symptoms and motor complications coupled with the inability to halt or slow disease progression may result in uncertainty and psychological stress. Evidence is lacking regarding biological mechanisms and symptom outcomes of uncertainty and psychological stress in PD. As such, 80 men and women diagnosed with PD after the age of 49 were recruited to participate in this study. Data specific to characteristics that may contribute to uncertainty and psychobehavioral measures of uncertainty, appraisal, psychological stress, and symptom outcomes of motor symptoms, pain, and fatigue were collected. Biological measures of neuropeptide Y (NPY) and cytokines were obtained. The results revealed that participants perceived a moderate level of illness uncertainty. Uncertainty correlated significantly with motor symptoms, pain severity, and pain interference and predicted more severe pain severity and pain interference. Psychological stress correlated significantly with motor symptoms, pain severity, pain interference, and fatigue and predicted more severe symptoms across all outcomes. NPY was positively correlated with threat appraisals and psychological stress. Cytokines were below the level of detection in this sample, and not used beyond descriptive analyses. In summary, this study found uncertainty and psychological stress contributed to more severe symptom outcomes in PD. This knowledge may be used to guide future studies aimed at further elucidating biobehavioral symptom and health outcomes of uncertainty and psychological stress in PD. It will also facilitate the development of interventions specifically targeted to uncertainty and psychological stress for the ultimate purpose of improving symptom management, health outcomes, and disease progression in PD.

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32

Ma, Wai-lung, and 馬惠龍. "The role of stress tolerance on marine invasive mussels." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2013. http://hdl.handle.net/10722/196040.

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Marine bioinvasion has been increasing exponentially due to intensive human activities. To manage the threats posed by marine bioinvasion, it is important to understand the key factors for invasion success. Stress tolerance is thought to play an important role in the invasion process, however, little is known of the nature of this tolerance, particularly whether stress tolerance is species- or population-specific. To determine this, laboratory experiments were conducted to investigate differential tolerance of populations of a cosmopolitan marine invasive mussel, Perna viridis, and whether stress tolerance can be altered through pre-selection of individuals. Comparisons were firstly made between two local P. viridis populations from the intertidal and subtidal zones to test if stress tolerance was population-specific. Individuals from the intertidal population had higher baseline heart rates, lower critical salinity values, Scrit, for cardiac activity and longer survival duration at low salinity than individuals from the subtidal population, supporting the presence of population level differences in stress tolerance. Mortality of P. viridis was also compared at sites in both their introduced range (Hong Kong) and native range (Indonesia) which revealed that individuals from the Hong Kong population were more stress tolerant than their native counterparts in Indonesia. Using the same experimental approach, the effect of pre-selection to stress (a prior pre-selection to hypoxia and a subsequent exposure to heat) showed that stress tolerance can be enhanced by pre-selection. The second part of this study investigated whether invasive mussels, Brachidontes variabilis and P. virdis, were more stress tolerant than the native, non-invasive, Septifer virgatus. Laboratory experiments compared the Scrit as well as critical temperature, Hcrit for cardiac activity. Mortality and byssus thread production were also measured in a factorial design with different combinations of temperature (16, 24 and 32 °C) and salinity (8, 16, 32 p.s.u) for 15 days. The two invasive mussels had a higher Hcrit and lower Scrit, which indicated a higher stress tolerance, than the non-invasive mussel. The mortality rate of P. viridis was faster than in B. variabilis and S. virgatus at 8 p.s.u. whereas S. virgatus was the only mussel that exhibited mortality in the medium hyposalinity (16 p.s.u.) and showed much slower byssus attachment than the invasive mussels, suggesting that the invasive mussels are more stress tolerant to heat and medium hyposalinity than the non-invasive species. Overall, stress tolerance proved to be higher in the invasive than non-invasive species and was also population-specific with higher stress tolerance in the invasive population, which may be attributed to the selection of more tolerant individuals during the invasion process. Such a process may occur when founding individuals successfully pass through an invasion process, which may increase the overall mean population-level of stress tolerance and explain why invasive species are generally more stress tolerant than native species. Thus stress tolerance plays an important role in invasion success and invasive species with high stress tolerance may be favoured by climate change, including ocean warming and increased precipitation, which may extend their current distribution range.
published_or_final_version
Biological Sciences
Master
Master of Philosophy

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33

Jadalla, Baraa Mohamed Ibrahim Soliman. "Phytochemical and biological studies of Helichrysum cymosum." University of the Western Cape, 2020. http://hdl.handle.net/11394/8264.

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Masters of Science
Diabetes mellitus (DM) is well known as a group of systemic metabolic disorders with a considerable mortality rate around the world. Hyperglycemia is the main consequence of DM, which results from the shortage in insulin production or degradation of produced insulin. Other internal and external factors including obesity, oxidative stress, and sedentary lifestyle have been also suggested as the causes of DM. Among the well-known existing types of DM, type 1 and 2 are the most common. Treatment of type 1 necessitates insulin injection, while type II can be controlled by physical exercises, diet control in addition to different synthetic antidiabetic drugs. However, their effectiveness is restricted because of the high cost and unfriendly side effects. There is a significant need for producing alternative and more bioactive antidiabetic drugs from natural sources. Natural products are a well-known source for the discovery of new scaffold for drugs discovery, and South Africa is one of the most important megaflora with a high percentage of endemism. South Africa is home to about 245 species of Helichrysum species, which are generally rich sources of secondary metabolites, especially flavonoids, which give them a great value for global acceptability and wide application in the pharmaceutical fields as antibacterial, anti-inflammatory, antioxidant, and antidiabetic agents. The phytochemical investigation of the methanolic extract of H. cymosum resulted in the isolation and identification of seven pure compounds (1-7). Structural characterization of these isolated compounds was conducted using 1D NMR, in comparison with reported spectroscopic data. The in vitro bio-evaluation of H. cymosum against alpha-glucosidase shown that 5 exhibited the highest alpha-glucosidase inhibitory activity with IC50 value of 13 μM, followed by 7 and 3 with IC50 values of 18.16 μM and 44.4 μM respectively. Additionally, strong total antioxidant capacities were displayed by 6 and 2 as ORAC (122.86 ± 0.7 and 91.70 ± 0.4 μM TE/mL) respectively as well as 5 and 7 as FRAP (1006.34 ± 1.7; 977.79 ± 0.8) μM AAE/g. This is the first scientific report to be carried out on alpha-glucosidase inhibitory activities and antioxidant capacities of H. cymosum constituents. The findings suggest that these compounds might become prominent natural candidates to inhibit alpha-glucosidase as well as oxidative stress related to diabetes with the prospect to be employed in the formulation of diabetes drugs upon further biological studies.

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Kilaru, Aruna. "Fatty Acid Ethanolamide Metabolism Influences Growth and Stress Responses." Digital Commons @ East Tennessee State University, 2014. https://dc.etsu.edu/etsu-works/4773.

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35

Asker, Mohammed. "Real-time measurement of locus coeruleus (LC) activity during eating and mild stress with fiber photometry." Thesis, Högskolan i Skövde, Institutionen för biovetenskap, 2019. http://urn.kb.se/resolve?urn=urn:nbn:se:his:diva-17138.

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Stress has been always associated with a deviating than normal feeding behavior. Both over-eating and under-eating accompanied by altered food choice towards palatable food have been reported in response to stress. The neuronal pathways that link stress with eating are still unclear. Locus Coeruleus (LC) is the main endogenous norepinephrine (NE) secreting nucleus. It lies in the center of the stress response mediating arousal state. LC-NE nucleus with its widespread innervations throughout the brain can modulate brain mechanisms linked with motivation towards food. In this study, the aim was to study the activity of NE neurons in the LC in relation to stress and food intake. The hypothesis was that NE neurons are activated by mild stressors and that this activity drives food intake. Because the association between LC activity and food intake is observational by nature, it is not expected to demonstrate a causal link but to show findings consistent with this hypothesis. Another aim was to standardize the photometry measurements and an analysis paradigm. In response to a stressor, animals showed freezing behavior, with photometry recordings displaying a significant reduction in Ca+2 signals right after the distressing stimulus. When a stressor preceded food intake, LC-NE activity significantly decreased right after the first meal the effect that did not last to the second meal with no difference between chow and palatable food. These results highlight the involvement of LC-NE in modulating feeding behavior by integrating environmental cues and internal needs. Future investigations of distinct, projection-defined, LC-NE sub-populations may reveal more specific food and stress interactions.

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Johnson, Lars. "Affective disorders in a stress-vulnerability perspective : a clinical, biological and psycho-social study /." Stockholm, 2002. http://diss.kib.ki.se/2002/91-7349-396-1/.

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37

Lam, Dennis, and 林勁行. "A study of biological role of reactive oxygen species in cellular response in stress." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2012. http://hub.hku.hk/bib/B47869604.

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When proteins are unable to fold properly in the endoplasmic reticulum (ER), the resultant formation of misfolded proteins causes stress of the ER. Cells with ER stress often have a higher abundance of reactive oxygen species (ROS). Previous studies suggest that ROS could aggravate ER stress by further disrupting the ER protein folding process. More recent studies suggest that the unfolded protein response signaling pathways activated by ER stress could lead to the production of ROS. Such studies lead to the hypothesis that ER stress could be promoted by ROS, and vice versa. The aim of the present study is to test the above hypothesis by studying how ROS could be generated in ER-stressed cells. This is followed by investigating if ROS could increase or decrease the level of ER stress in cells. Finally, the extent of ER stress induced cell death in the presence and absence of ROS is assessed. The treatment of HeLa cells with tunicamycin (Tm), a common ER-stress inducing agent, resulted in the elevation of intracellular ROS that could be detected with the ROS-reactive probe dichlorodihydrofluorescein (DCF), but not dihydroethidium which is relatively specific towards superoxide anion. The Tm-induced elevation of ROS could be prevented by co-incubation of cells with thiol reductants such as dithiothreitol and N-acetylcysteine but not with the free radical scavenger ascorbate. The tunicamycin-induced elevation of ROS level could also be prevented by the over-expression of catalase in HeLa. These data is consistent with the idea that hydrogen peroxide is a major form of ROS produced in Tm-treated cells. In addition to elevation of ROS level, HeLa cells treated with tunicamycin also resulted in the phosphorylation of PERK and eIF2α, and the splicing of XBP-1. In the presence of cycloheximide to inhibit protein synthesis so as to deplete protein substrates for folding in the ER, tunicamycin-induced ER stress was greatly minimized as was evident by the absence of both the phosphorylation of PERK and splicing of XBP-1. However, the phosphorylation of eIF2α and elevation of DCF-detectable ROS remained unaffected. The cycloheximde-resistant phosphorylation of eIF2α could be prevented when cells were co-treated with thiol reductants, or upon the over-expression of catalase. These data suggest that the production of ROS in Tm-treated cells does not require the presence of ER stress as a prerequisite. Furthermore, the ROS so produced could induce phosphorylation of eIF2α without the need to cause ER stress in the first place. The quenching of ROS through the use of thiol reductants, or the over-expression of catalase, had no effect on inhibition of protein synthesis in cells treated with tunicamycin. However, the extent of cell death was significantly increased. The data obtained in this study is not consistent with the idea that ROS is a downstream product of ER stress, capable of inducing more ER-stress by a feedback mechanism. Therefore, a mutually enhancing effect between ER stress and ROS may not exist. The ROS found in stressed cells may serve to extend cellular survival under the condition of continuous stress.
published_or_final_version
Biochemistry
Doctoral
Doctor of Philosophy

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38

Chlup, Paul H. "Biological and hydrodynamic stress influences on brewing yeast strains' physiological status during beer production." Thesis, Heriot-Watt University, 2008. http://hdl.handle.net/10399/2195.

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Biological hydrodynamic stress influences on yeast and the resulting consequences on beer stability have been investigated. Yeast cells subjected to stress during beer production have a negative effect on its physiological status. Cell wall and membrane constituents determine the cells capacity to adapt to stress. A relationship has been established that yeast cell wall mannan, an unfilterable haze constituent, as a function of hydrodynamic stress exposure, is released from the cell wall while concurrently, particle size in the supernatant, and beer haze increased. In high gravity wort (20 °Plato), compared to lower gravity wort (12 °Plato), there is an increase in the number of damaged cells and lower intracellular glycogen and trehalose levels, indicating stressed cells. Cell viability and intracellular pH decreased due to processing conditions encountered during yeast cropping with a centrifuge. Furthermore, yeast intracellular glycogen and trehalose levels were depleted as a result of centrifugation. A comprehensive evaluation of yeast fermentation predictors such as viability, damaged cells, intracellular pH (PHi), intracellular glycogen and trehalose is of vital importance. The flow cytometer is able to rapidly reform numerous accurate yeast physiology analyses, providing information that will optimize yeast management circuits, improve fermentation efficiency resulting in enhanced beer quality.

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Lawler, Jennifer Rae Noelle 1962. "Eichhornia crassipes (Mart) Solms in wastewater treatment: Reducing low-temperature stress." Thesis, The University of Arizona, 1989. http://hdl.handle.net/10150/291651.

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Studies were carried out from July 1988 to August 1989 to assess the growth and winter survival of water hyacinth, Eichhornia crassipes (Mart.) Solms, in treatment of secondary domestic wastewater in Tucson, Arizona. Percent of surviving overwintered plants for the following frost protection treatments from November 1988 to March 1989 was: 25 (control), 48 (plastic tarps), 70 (sprinklers), 34 (fog) and 76 (greenhouse). Both control plants and protected plants had longer roots at the effluent end of the ponds than the influent ends during winter months. Greenhouse-protected plants had greater root and entire plant lengths, and greater fresh and dry weights. Dry weight per unit area (kg m⁻²) was higher for greenhouse plants though all protected plants showed decline in dry weight per unit area with temperatures below 10 C. Qualitative observations indicated that protected plants showed less chlorosis and necrosis from low temperatures than control plants, however, plants in all frost protected treatments experienced low temperature stress. Aphids were seen in some of the ponds throughout the study and contributed to severe lamina and petiole damage.

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White, James David. "A controlled comparative investigation of large group therapy for generalised anxiety disorder - "stress control"." Thesis, University of Glasgow, 1989. http://theses.gla.ac.uk/3708/.

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One hundred and nine generalised anxiety disorder (GAD) patients, referred by their General Practitioners to a clinical psychology primary care service, were assigned to either Cognitive, Behavioural, Cognitive-behavioural, Placebo or Waiting List conditions. `Stress Control' large group therapy combined didactic therapy with a workshop model and emphasised the aim of turning patients into their own `therapists' in order to enable them to deal with present and future problems. Patients were thus encouraged to view Stress Control as an `evening class' rather than `group therapy'. Measures of treatment process and outcome were obtained mainly from self-report instruments. Follow-up data were collected at six months post-treatment. At post-therapy, all active therapy conditions and, against expectation, the Placebo condition had shown significant time within treatment group change. The active therapy conditions, and to a lesser extent, the Placebo condition, were significantly different to the Waiting List condition, which, overall showed no evidence of improvement. At follow-up the active therapy condition generally enhanced therapy gains while the placebo condition maintained therapy gains. Process measures did not, with the exception of self-statement change, differentiate between the groups. Noted variable response in the main analyses was somewhat explained by various sub-group analyses. There appeared to be little benefit in dividing patients into those who experienced panic and those who did not. There was some evidence that `matching' patients to therapy, i.e. cognitive responders to cognitive therapy was of value at post-therapy although differences generally disappeared at follow-up. Synchronous change was associated with enhanced performance. Finally, attempts to predict response to Stress Control by a comparison of responders and non-responders were attempted and the results assessed in terms of clinical as opposed to statistical significance. The results of the present study are discussed with reference to other treatment outcome studies and an attempt to produce a model to account for the similar effects found across treatment conditions. The implications of these findings and some suggestions for future research for GAD and other diagnostic categories are discussed.

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Frost, Matthew Thomas. "The measurement of 3 nitrotyrosine in biological samples and its application to the assessment of protein nitration in disease." Thesis, King's College London (University of London), 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.249697.

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42

Koertge, Jenny. "Vital exhaustion and coronary artery disease in women : biological correlates and behavioral intervention /." Stockholm, 2003. http://diss.kib.ki.se/2003/91-7349-564-6/.

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43

Laresgoiti, Servitje Servitje Estibalitz. "Effect of Stress, Emotional Lability and Depression on the Development of Pregnancy Complications." ScholarWorks, 2011. https://scholarworks.waldenu.edu/dissertations/1074.

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Chronic stress and other emotional factors may have relevant impacts on pregnancy outcomes because they are related to neuroendocrine changes that lead to alterations in immunomodulation during pregnancy. In this quantitative prospective cross-sectional study, the relationship of emotional lability, depression, and stress during pregnancy and the development of preterm labor, preeclampsia, placental abruption, and low birth weight for gestational age babies was examined. Additionally, social support scores were compared to levels of stress/anxiety, depression, and emotional lability in pregnant women. Two hundred and forty two pregnant women who received prenatal services at the National Institute of Perinatology in Mexico City were evaluated during the 2nd or 3rd trimester of pregnancy and followed until pregnancy termination. Logistic regression analyses showed that being single significantly predicted preeclampsia and preterm birth, and the presence of social support significantly decreased the likelihood of preterm birth development. In the logistic regression model, family income significantly predicted the development of abruptio placentae. MANCOVA results revealed a significant difference among the social support categories on the combined dependent variables (stress/anxiety, depression, and emotional lability). The ANCOVA reported significant differences between social support scores, and stress/anxiety and depression scores. ANCOVA also showed significant differences between the number of pregnancies and stress scores. A 2X2 factorial analysis of variance showed a significant main effect of stress and depression on newborn weight. By promoting awareness of the importance of emotional factors during pregnancy among healthcare workers and pregnant women, this study contributed to positive social change.

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Snowden, Kimberley Cathryn. "The molecular response of wheat roots to aluminium stress." Thesis, University of Auckland, 1994. http://hdl.handle.net/2292/1967.

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Aluminium (Al) toxicity to plants is a significant problem, limiting agricultural production in up to 40% of the world's arable soils. In spite of a large amount of research, there is still no consensus on the physiological mechanisms of Al toxicity in plants. In addition, very little is known about the molecular response of plants to Al stress. This body of research was aimed at identifying the changes in gene expression that occurred in the root tips of plants that had been stressed with Al. A cDNA library made from the root tips of Al-treated wheat (Triticum aestivum L., cultivar Warigal) plants was differentially screened to identify clones whose expression was induced by Al stress. Seven cDNA clones, representing five different genes were identified as being induced in the presence of Al. Initial sequencing and northern analysis revealed that none of the clones isolated were full-length, and that some contained multiple cloning adaptors at their 5' ends. A new cDNA library was then constructed from the root tips of Al-treated Warigal plants, and homologues to each of the original five genes were isolated. These five clones were named wali1 to wali5 (for wheat aluminium induced). Northern analysis showed that wali1, -3 and -5 were induced 24 to 96 h after Al treatment, and their expression declined when the Al was removed. wali4 had a similar pattern of expression with a transient increase in expression also observed after 0.5 h of Al stress. Each of these four genes was induced by inhibitory concentrations of Al in two wheat cultivars - Warigal, an Al-sensitive cultivar, and Waalt, an Al-tolerant cultivar, - and also in two inbred lines of wheat, RR (Al-tolerant) and SS (Al-sensitive). The fifth gene (wali2) had a bimodal pattern of induction, and was induced by Al only in the Al-sensitive Warigal and the Al-tolerant RR. The nucleotide sequence of each of the wali clones was determined, and the databases were searched for homologous sequences. Wali1 was found to be homologous to a group of metallothionein-like proteins (MLPs) from plants, and wali4 was homologous to phenylalanine ammonia-lyase (PAL). wali3 and wali5 encode related, cysteine-rich proteins with homology to Bowman-Birk proteinase inhibitors, and wali2 encodes a novel protein with a repeating motif of cysteine amino acids. The induction of the wali genes was investigated in response to a number of other stresses through northern analysis. The expression of wali1, -3, -4 and -5 was induced in root tips of wheat after 2 d treatments with toxic levels of all other metals tested (Cd, Fe, Zn, Cu, Ga, In and La). The expression levels of wali1, -3, -4, and -5 also increased in the root tips of plants grown in the presence of low levels of Ca (10μM). The transcript levels of wali1, -3 and -5 increased in wounded leaf and root tissue, whereas the transcript levels of wali4 increased only in wounded leaves. The expression of wali2 was greatly reduced by low concentrations of Ca, and showed no induction, or a variable response with most of the other treatments. The site of expression of wali1, -2, -3 and -5 in root tips (and wali1 also in leaf tissue) was identified using in situ hybridisation. Wali1 was expressed predominantly in the meristematic tissue of the root tip, while wali3 and wali5 were expressed predominantly in the cortical tissue of the root. wali2 expression was detected primarily in the epidermis and root cap. Some changes in the site of expression of these genes were evident in the roots of Al-treated plants. In leaf tissue, wali1 expression was found in the mesophyl1 layer of cells. The coding sequences for wali1,-2,-3 and -5 were each cloned into the bacterial expression vector pGEX-2T. The resultant fusion proteins between glutathione S-transferase (GST) and the walis were then successfully purified from E coli. Antibodies were made to the wali1-GST fusion protein and purified by immunoaffinity chromatography. However, when used in western analysis, no specific bands corresponding to the native wali1 protein were identified. The wali2-GST protein was used in a south-western procedure to determine if the protein was capable of binding DNA, but no DNA binding to this protein was detected under the conditions tested. The wali3 and wali5 fusion proteins were tested in proteinase inhibitor assays, where no inhibition of either trypsin or chymotrypsin was detected. It is possible that the native wali3 and wali5 proteins may not function as proteinase inhibitors, or that the lack of activity detected for the fusion proteins may be due to incorrect folding or processing in the bacterial system. This research constitutes the first identification of plant genes whose expression is increased by Al stress. The genes identified are also induced in response to other environmental and nutrient stresses, indicating that they form part of the plant's general response to stress.
Appendix 4 restricted.

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Bratt, Katharina. "Secondary plant metabolites as defence against herbivores and oxidative stress : Synthesis, isolation and biological evaluation." Doctoral thesis, Uppsala University, Department of Chemistry, 2000. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-1074.

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In this thesis the isolation, synthesis and biological evaluation of natural defense compounds against herbivores or oxidative stress is discussed.

The first part concerns the metabolites of platyphylloside ((5S)-5-hydroxy-1,7-bis-(4-hydroxyphenyl)-3-heptanone-5-O-β-D-glucopyranoside), a phenolic glucoside found in birch (Betula pendula) that possess digestibility inhibiting activity in herbivores. The structure-activity relationship of platyphylloside analogues were investigated regarding to stereochemistry and substitution pattern on the aromatic rings. The metabolites formed in vitro in rumen fluid were synthesized and the active metabolite determined as (R)-centrolobol (1,7-bis-(4-hydroxyphenyl)-3-heptanol). Treatment of mice and rats with rac-centrolobol did not effect either food intake or body weight. Effect of platyphylloside in moose was also investigated, and the results indicate that there was an in vivo digestibility reducing activity.

The second part concerns naturally occurring antioxidants. Avenanthramides is a class of phenolic antioxidants found in oat (Avena sativa). Avenanthramides derived from either anthranilic acid or 5-hydroxyanthranilic acid were evaluated for their antioxidative capacity and quantified in oat extracts. Avenanthramides derived from 5-hydroxyanthranilic acid possessed higher activity than those from anthranilic acid. The order of reactivity depending on substitution pattern on the phenolic moiety was found to be 4-hydroxy < 4-hydroxy-3-methoxy < 3,5-dimethoxy-4-hydroxy and 3,4-dihydroxy. A synthesis towards antioxidative compounds such as 4-deoxycarbazomycin was developed.

The third part concerns the isolation of compounds from Lodgepole pine (Pinus contorta) with antifeedant activity against pine weevil (Hylobius abietis). Two compounds possessing high activity were isolated and identified.

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Marin, Teresa J. "Specific features of stressful experiences, interpersonal sensitivity, and biological stress mediators in children and adolescents." Thesis, University of British Columbia, 2010. http://hdl.handle.net/2429/29453.

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This thesis examines the associations between stressful experiences and biological mediators in young people, with an emphasis on specific features of the stressor (such as duration and emotion-eliciting qualities) and the moderating role of dispositional interpersonal sensitivity. Study 1 examined the effects of major life events, chronic interpersonal stress, and the interaction between the two among 104 adolescent women. The biological outcomes were cortisol output, the expression of glucocorticoid receptor (GR) mRNA, C-reactive protein (CRP), insulin, and glucose. Results indicated that neither life events nor chronic interpersonal stress was significantly associated with biological outcomes. However, adolescents who experienced the combination of a major life event and higher levels of chronic interpersonal stress showed increased cortisol output and decreased expression of GR mRNA. This indicates that the simultaneous exposure to both acute and chronic stress may be particularly detrimental. Study 2 aimed to replicate these findings among 71 youth with asthma. This study followed participants over 2 years. Life stress, asthma-relevant immune activity, and daily asthma symptoms were measured every 6 months. Findings were analyzed using hierarchical linear modeling (HLM). Similar to the study 1 findings, youth who were double-exposed to a major life event and chronic family stress showed increased production of asthma-relevant cytokines and increased symptom expression. Finally, study 3 examined the interaction between interpersonal sensitivity and life event dimensions of loss, danger, and humiliation among 144 adolescent women. Study outcomes included markers of early cardiovascular risk, such as blood pressure and indicators of systemic inflammation (serum CRP, serum interleukin-6, and stimulated IL-6). Life stress dimensions and biological outcomes were measured every 6 months over 2.5 years. HLM analyses indicated that interpersonal sensitivity moderated the relations of danger events to CRP and diastolic blood pressure, such that the biological response was amplified among interpersonally sensitive adolescents. Interpersonal sensitivity also interacted with loss events, and adolescents high on interpersonal sensitivity showed increased production of the pro-inflammatory cytokine IL-6 in the aftermath of major loss. Overall, findings indicate that stressor impact is a complex phenomenon that depends on specific properties of the stressor, as well as dispositional factors like interpersonal sensitivity.

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Thakor, Avnesh Sinh. "The role of oxidative stress in mediating the biological effects of Raman-silica-gold-nanoparticles." Thesis, University of Cambridge, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.610296.

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Bott, Charles Briddell. "Elucidating the Role of Toxin-Induced Microbial Stress Responses in Biological Wastewater Treatment Process Upset." Diss., Virginia Tech, 2001. http://hdl.handle.net/10919/26641.

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The overall hypothesis of this work is that the physiological microbial stress response could serve as a rapid, sensitive, and mechanistically-based indicator of process upset in biological wastewater treatment systems that receive sporadic shock loads of toxic chemicals. The microbial stress response is a set of conserved and unique biochemical mechanisms that an organism activates or induces under adverse conditions, specifically for the protection of cellular components or the repair of damaged macromolecules. Using traditional immunochemical analysis techniques, the heat shock protein, GroEL, was found to be induced in activated sludge cultures exposed to perturbations of chemicals at all concentrations tested (cadmium, pentachlorophenol, and acetone) or heat stress. As total cadmium concentrations increased above 5 mg/L, there was a significant and consistent increase in effluent volatile suspended solids concentrations from activated sludge sequencing batch reactors relative to unstressed controls, but there was no additional increase in GroEL levels. Stress proteins may serve as sensitive and rapid indicators of mixed liquor toxicity which can adversely impact treatment process performance, but GroEL may not be a good candidate protein for this purpose due to the lack of a dose/response relationship. Additionally, production of stress proteins did not explain the significant deflocculation upsets that were characteristic of many of the industrially-relevant chemicals tested, including pentachlorophenol and cadmium. Although the purpose of stress response mechanisms is protective at the cellular level, the effect may be disruptive at the macroscopic level in engineered bioreactor systems. The goal of the second research phase was to determine whether the bacterial glutathione-gated, electrophile-induced potassium efflux system is responsible for deflocculation observed due to shock loads of toxic electrophilic (thiol reactive) chemicals. The results indicate significant K+ efflux from the activated sludge floc structure to the bulk liquid in response to shock loads of 1-chloro-2,4-dinitrobenzene (CDNB), N-ethylmaleimide (NEM), 2,4-dinitrotoluene (DNT), 1,4-benzoquinone (BQ), and Cd2+ to a bench-scale sequencing batch reactor (SBR) system. In most cases, the stressor chemicals caused significant deflocculation, as measured by an increase in effluent volatile suspended solids (VSS), at concentrations much less than that required to reduce the maximum specific oxygen uptake rate by 50% (IC50). This suggests that electrophile-induced activated sludge deflocculation is caused by a protective bacterial stress mechanism (as hypothesized) and that the upset event may not be detectable by aerobic respirometry. More importantly, the amount of K+ efflux appeared to correlate well with the degree of deflocculation. The transport of other cations including sodium, calcium, magnesium, iron, and aluminum, either to or from the floc structure, was negligible as compared to K+ efflux. In bench-scale SBRs, it was also determined that the K+ efflux occurred immediately (within minutes) after toxin addition and then was followed by an increase in effluent turbidity. K+ efflux and deflocculation responses were similar for bench-scale SBRs and continuous-flow reactor systems, indicating that the periods of elevated exogenous substrate levels typical in SBR systems are not required to activate electrophile-induced K+ efflux or deflocculation. This also suggests that the initial and rapid efflux of K+ immediately following electrophile addition is the factor that leads to deflocculation, not the increase in bulk liquid K+. Sphingomonas capsulata, a bacterium consistent with that found in biological wastewater treatment systems, Escherichia coli K-12, and activated sludge cultures exhibited very similar dynamic efflux/uptake/efflux responses due to the electrophilic stressors, NEM and CDNB, and the thiol reducing agent, dithiothreitol (DTT). The polyether ionophore antibiotic, nigericin, was used to artificially stimulate K+ efflux from S. capsulata and activated sludge cultures. Thus, glutathione-gated K+ efflux (GGKE) activity may cause K+ release from the cytoplasm of activated sludge bacteria into the floc structure and extracellular polymeric substances (EPS) and then diffusion-limited transport into the bulk liquid. It was not possible to resolve the effect of the GGKE system on changes in bulk liquid or floc-associated pH. However, calculations indicate that the localized K+ concentration within the floc structure immediately after chemical stress is consistent with that known to induce floc disruption as a result of KCl addition. Using alkaline phosphatase as a periplasmic marker as well as fluorescent membrane-permeable and impermeable nucleic acid stains, it was determined that a negligible amount of the K+ efflux response was due to lysis of activated sludge microorganisms. The current results are very promising and are the first to suggest that activated sludge upset (i.e. deflocculation) may be caused by a specific protective stress response in bacteria.
Ph. D.

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Wolfgang, Curt Douglas. "A study of the biological function of ATF3 : stress inducibility, target promoters and functional consequences /." The Ohio State University, 2000. http://rave.ohiolink.edu/etdc/view?acc_num=osu148819244742789.

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Ghezzo, Alessandro <1962&gt. "The biological basis of autism spectrum disorders: evaluation of oxidative stress and erytrocyte membrane alterations." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2015. http://amsdottorato.unibo.it/7116/.

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This case-control study involved a total of 29 autistic children (Au) aged 6 to 12 years, and 28 gender and age-matched typically developing children (TD). We evaluated a high number of peripheral oxidative stress parameters, erythrocyte and lymphocyte membrane functional features and membrane lipid composition of erythrocyte. Erythrocyte TBARS, Peroxiredoxin II, Protein Carbonyl Groups and urinary HEL and isoprostane levels were elevated in AU (confirming an imbalance of the redox status of Au); other oxidative stress markers or associated parameters (urinary 8-oxo-dG, plasma Total antioxidant capacity and plasma carbonyl groups, erythrocyte SOD and catalase activities) were unchanged, whilst peroxiredoxin I showed a trend of elevated levels in red blood cells of Au children. A very significant reduction of both erythrocyte and lymphocyte Na+, K+-ATPase activity (NKA), a reduction of erythrocyte membrane fluidity, a reduction of phospatydyl serine exposition on erythrocyte membranes, an alteration in erythrocyte fatty acid membrane profile (increase in MUFA and in ω6/ω3 ratio due to decrease in EPA and DHA) and a reduction of cholesterol content of erythrocyte membrane were found in Au compared to TD, without change in erythrocyte membrane sialic acid content and in lymphocyte membrane fluidity. Some Au clinical features appear to be correlated with these findings; in particular, hyperactivity score appears to be related with some parameters of the lipidomic profile and membrane fluidity, and ADOS and CARS score are inversely related to peroxiredoxin II levels. Oxidative stress and erythrocyte structural and functional alterations may play a role in the pathogenesis of Autism Spectrum Disorders and could be potentially utilized as peripheral biomarkers.

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