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Investigation into the destructive and adaptive responses of neural cells to stressHasel, Philip January 2017 (has links)
Homeostasis within the neuro-glial unit is essential to the longevity of neurons. Conversely, loss of homeostasis, particularly of Ca2+ levels, of redox balance and of ATP, contribute to neuronal loss and dysfunction in many neurodegenerative and neurological disorders. This thesis is centred on better understanding the vulnerability of neurons to stress, as well as adaptive responses to these stresses. Since neurodegenerative conditions associated with Ca2+, redox and bioenergetic dyshomeostasis are often characterised by early dendritic pathology, I first studied dendritic vs. somatic responses of primary cortical neurons to these types of challenges in real-time. Using a wide range of genetically-encoded probes to measure Ca2+, ATP, NADH, glutathione and glutamate, I show that dendrites are selectively vulnerable to oxidative stress, excitotoxicity as well as to metabolic demand induced by action potential (AP) burst activity. However, I provide evidence that neurons undergoing energetically demanding AP burst activity can adjust their metabolic output by increasing mitochondrial NADH production in a manner dependent on the mitochondrial calcium uniporter (MCU), as well as increase their capacity to buffer their intracellular redox balance. Finally, I have studied transcriptional programs in astrocytes triggered by neurons and neuronal activity to better understand adaptive signaling between different cell types in the neuro-glial unit. I developed a novel system combining neurons and astrocytes from closely-related species, followed by RNA-seq and in silico read sorting. I uncovered a program of neuron-induced astrocytic gene expression which drives and maintains astrocytic maturity and neurotransmitter uptake function. In addition I identified a novel form of synapse-to-nucleus signaling, mediated by glutamatergic activity and acutely regulating diverse astrocytic genes involved in astrocyte-neuron metabolic coupling. Of note, neuronal activity co-ordinately induced astrocytic genes involved in astrocyte-to-neuron thyroid hormone signaling, extracellular antioxidant defences, and the astrocyte-neuron lactate shuttle, suggesting that this non cell-autonomous signaling may form part of the homeostatic machinery within the neuro-glial unit.
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Adaptive responses of salmonella enterica serovar enteritidis ATCC 4931 biofilms to nutrient laminar flow and benzalkonium chloride treatmentIllathu, Anilkumar Mangalappalli 12 December 2007
<i>Salmonella enterica serovar Enteritidis</i> is an important biofilm-forming food-borne pathogen. This study examined the adaptive responses of <i>Salmonella serovar Enteritidis</i> biofilms to different environmental conditions such as flow velocity and benzalkonium chloride (BC) treatment. The influence of a 10-fold difference in nutrient laminar flow velocity on the dynamics of biofilm formation and protein expression profiles was compared. The mode of development and architecture of low-flow and high-flow biofilms were distinct. Exopolymer composition of the two biofilms was also different. However, no major shift in protein expression was seen between the biofilms, nor were there any stress response proteins involved. The biofilms altered their architecture in response to flow, presumably assuming a structure that minimized overall biofilm stress. An empirically-determined shear-inducing flow was applied on high-flow biofilms, fractionating the biofilms into shearable and non-shearable regions. Length:width indices of cells from the two biofilm regions, as well as planktonic cells from biofilm effluent and continuous culture were determined to be 3.2, 2.3, 2.2, and 1.7, respectively. Expression of proteins involved in cold-shock response, adaptation, and broad regulatory functions in the shearable region, and expression of protein involved in heat-shock response and chaperonin function in the non-shearable region indicated that the physiological status of cells in two biofilm regions was also distinct. The development of biofilm adaptive resistance to BC was then examined. Adapted biofilms survived a lethal BC challenge and re-grew, whereas unadapted biofilms did not. Proteins up-regulated following adaptation included those involved in energy metabolism, amino acid and protein biosynthesis, nutrient-transportation, adaptation, detoxification, and 1,2-propanediol degradation. A putative universal stress protein was also up-regulated. Cold-shock response, stress response, and detoxification are suggested to play roles in adaptive resistance to BC. Functional differences in adaptive response and survival of plankonic and biofilm cells adapted to BC were also studied. The proportion of BC-adapted biofilm cells that survived a lethal BC exposure and heat-shock was significantly higher than that of BC-adapted planktonic cells. Enhanced biofilm-specific up-regulation of various proteins, coupled with alterations in cell surface roughness and shift in fatty acid composition are proposed to function in the enhanced survival of BC-adapted biofilm cells, relative to BC-adapted planktonic cells.<p>It is concluded that biofilms adapt to the stress conditions by means of community, cellular, and sub-cellular level responses. These adaptive responses help the biofilms to enhance their ability for survival in the nature, especially those formed in critical environments such as healthcare facilities, the food industry, and households.
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Adaptive responses of salmonella enterica serovar enteritidis ATCC 4931 biofilms to nutrient laminar flow and benzalkonium chloride treatmentIllathu, Anilkumar Mangalappalli 12 December 2007 (has links)
<i>Salmonella enterica serovar Enteritidis</i> is an important biofilm-forming food-borne pathogen. This study examined the adaptive responses of <i>Salmonella serovar Enteritidis</i> biofilms to different environmental conditions such as flow velocity and benzalkonium chloride (BC) treatment. The influence of a 10-fold difference in nutrient laminar flow velocity on the dynamics of biofilm formation and protein expression profiles was compared. The mode of development and architecture of low-flow and high-flow biofilms were distinct. Exopolymer composition of the two biofilms was also different. However, no major shift in protein expression was seen between the biofilms, nor were there any stress response proteins involved. The biofilms altered their architecture in response to flow, presumably assuming a structure that minimized overall biofilm stress. An empirically-determined shear-inducing flow was applied on high-flow biofilms, fractionating the biofilms into shearable and non-shearable regions. Length:width indices of cells from the two biofilm regions, as well as planktonic cells from biofilm effluent and continuous culture were determined to be 3.2, 2.3, 2.2, and 1.7, respectively. Expression of proteins involved in cold-shock response, adaptation, and broad regulatory functions in the shearable region, and expression of protein involved in heat-shock response and chaperonin function in the non-shearable region indicated that the physiological status of cells in two biofilm regions was also distinct. The development of biofilm adaptive resistance to BC was then examined. Adapted biofilms survived a lethal BC challenge and re-grew, whereas unadapted biofilms did not. Proteins up-regulated following adaptation included those involved in energy metabolism, amino acid and protein biosynthesis, nutrient-transportation, adaptation, detoxification, and 1,2-propanediol degradation. A putative universal stress protein was also up-regulated. Cold-shock response, stress response, and detoxification are suggested to play roles in adaptive resistance to BC. Functional differences in adaptive response and survival of plankonic and biofilm cells adapted to BC were also studied. The proportion of BC-adapted biofilm cells that survived a lethal BC exposure and heat-shock was significantly higher than that of BC-adapted planktonic cells. Enhanced biofilm-specific up-regulation of various proteins, coupled with alterations in cell surface roughness and shift in fatty acid composition are proposed to function in the enhanced survival of BC-adapted biofilm cells, relative to BC-adapted planktonic cells.<p>It is concluded that biofilms adapt to the stress conditions by means of community, cellular, and sub-cellular level responses. These adaptive responses help the biofilms to enhance their ability for survival in the nature, especially those formed in critical environments such as healthcare facilities, the food industry, and households.
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Human Abuses of Coral Reefs- Adaptive Responses and Regime TransitionsNordemar, Ingrid January 2004 (has links)
<p>During the last few decades, coral reefs have become a disappearing feature of tropical marine environments, and those reefs that do remain are severely threatened. It is understood that humans have greately altered the environment under which these ecosystems previously have thrived and evoloved. Overharvesting of fish stocks, global warming and pollution are some of the most prominent threats, acting on coral reefs at several spatial and temporal scales. Presently, it is common that coral reefs have been degraded into alternative ecosystem regimes, such as macroalgae-dominated or sea urchin-barren. Although these ecosystems could potentially return to coral dominance in a long-term perspective, when considdering current conditions, it seems likely that they will persist in their degraded states. Thus, recovery of coral reefs cannot be taken for granted on a human timescale. Multiple stressors and disturbances, which are increasingly characteristic of coral reef environments today, are believed to act synergistically and produce ecological surprises. However, current knowledge of effects of compounded disturbances and stress is limited. Based on five papers, this thesis investigates the sublethal response of multiple stressors on coral physiology, as well as the effects of compounded stress and disturbance on coral reef structure and function. Adaptive responses to stress and disturbance in relation to prior experience are highlighted. The thesis further explores how inherent characteristics (traits) of corals and macroalgae may influence regime expression when faced with altered disturbance regimes, in particular overfishing, eutrophication, elevated temperature, and enhanced substrate availability. Finally, possibilities of affecting the resilience of macroalgae-dominaed reefs and shifting the community composition towards a coral-dominated regime are explored.</p>
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Human Abuses of Coral Reefs- Adaptive Responses and Regime TransitionsNordemar, Ingrid January 2004 (has links)
During the last few decades, coral reefs have become a disappearing feature of tropical marine environments, and those reefs that do remain are severely threatened. It is understood that humans have greately altered the environment under which these ecosystems previously have thrived and evoloved. Overharvesting of fish stocks, global warming and pollution are some of the most prominent threats, acting on coral reefs at several spatial and temporal scales. Presently, it is common that coral reefs have been degraded into alternative ecosystem regimes, such as macroalgae-dominated or sea urchin-barren. Although these ecosystems could potentially return to coral dominance in a long-term perspective, when considdering current conditions, it seems likely that they will persist in their degraded states. Thus, recovery of coral reefs cannot be taken for granted on a human timescale. Multiple stressors and disturbances, which are increasingly characteristic of coral reef environments today, are believed to act synergistically and produce ecological surprises. However, current knowledge of effects of compounded disturbances and stress is limited. Based on five papers, this thesis investigates the sublethal response of multiple stressors on coral physiology, as well as the effects of compounded stress and disturbance on coral reef structure and function. Adaptive responses to stress and disturbance in relation to prior experience are highlighted. The thesis further explores how inherent characteristics (traits) of corals and macroalgae may influence regime expression when faced with altered disturbance regimes, in particular overfishing, eutrophication, elevated temperature, and enhanced substrate availability. Finally, possibilities of affecting the resilience of macroalgae-dominaed reefs and shifting the community composition towards a coral-dominated regime are explored.
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Emotion Perception in Asperger's Syndrome and High-functioning Autism: The Importance of Diagnostic Criteria and Cue IntensityMazefsky, Carla Ann 01 January 2004 (has links)
Asperger's syndrome (AS) is a pervasive developmental disorder that is associated with marked social dysfunction. Deficits in the perception of nonverbal cues of emotion may be related to this social impairment. Research has indicated that children with autism are limited in their emotion perception abilities, but studies that have addressed this issue with individuals with AS or high-functioning autism (HFA) have yielded inconsistent findings. These inconsistencies may be related to methodological differences across studies including diagnostic criteria and failure to consider the intensity of the emotion cues. It was hypothesized that children with AS and HFA would both have deficits in emotion perception compared to typically-developing children. However, children with HFA were expected to have an even greater emotion perception deficit than children with AS and this difference was hypothesized to be most pronounced for low intensity cues of emotion. It is important to clarify whether individuals with AS and HFA differ in emotion perception because most studies of this skill combine them into one group or use poorly defined diagnostic criteria. This study examined the ability of 30 8- to 15-year-old children with either AS or HFA to perceive emotion from high and low intensity cues. In order to address limitations with the differential validity of the DSM-IV criteria for AS, diagnoses were based on diagnostic criteria proposed by Klin et al. (in press). A researcher who was blind to diagnosis administered a test that presented low and high intensity cues of emotion in photographs of facial expression and audiotapes of tone of voice. Comparison of the emotion perception accuracy of children with AS to the normative means of this instrument for typically-developing children did not reveal any significant differences. In contrast, the children with HFA were significantly less accurate in their perception of facial expressions and tone of voice than the normative sample and the participants with AS. Contrary to expectations, IQ was significantly related to emotion perception accuracy. After controlling for IQ, the difference in perception of facial expressions between children with AS and HFA was not significant. On the other hand, cue intensity moderated the relation between diagnosis and emotion perception accuracy for tone of voice even after IQ was taken into account. Children with AS perceived high and low intensity tone of voice cues with similar accuracy, but children with HFA had significantly poorer performance on the low intensity tone of voice cues. Although emotion perception accuracy was related to better adjustment, it was not correlated with the most sensitive measure of current social functioning. This suggests that even when children with AS or HFA perceive cues correctly, they may not know how or be able to properly integrate them for adaptive responses in social interaction. The findings have important implications for understanding inconsistencies in past research and identifying future directions.
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Kulturskolans ramar : Kulturskolelärares upplevelser av stress i arbetslivetBritts, Oliver Benjamin January 2024 (has links)
Music teachers are often exposed to high levels of stress which can oftentimes lead to feelings of dejection, anxiety, and depression. Teachers who work in Swedish Community Schools of Music and Arts have reported an increase in the levels of stress the last 5 years. There’s a dearth of scientific research in this area despite these reports. Hence, the aim of this study is to illuminate the stress-related experiences of music teachers who work within the Swedish Community Schools of Music and Arts and their description of the challenges associated with their profession. In this study organizational structural frame factors are explored to find how the frameworks can cause stressors to form, which in turn leads to stress. The results show how a variety of stressors were caused by different frame factors like insufficient time for preparation, working hours, organizational volatility regarding resources and policies, and municipal unidirectional communication. Some of the stressors were found to prompt adaptive responses, preventing the emergence of new stressors, while others were identified as contributing to a recursive cycle of stressor creation when the teachers expressed an inability to control the stressors. / Hög stressintensitet är något som musiklärare får uppleva dagligen och det kan i många fall vara det som orsakar nedstämdhet, ångest, och depression. Kulturskolelärare är en grupp som rapporterat en ökning av stressintensitet över de senaste 5 åren. Trots detta finns det väldigt lite forskning som berör just ämnet stress i kulturskolan. Därför ämnar detta arbete belysa musiklärares beskrivna upplevelser av stress kopplat till kulturskolearbete. I denna studie undersöks de ramfaktorer som beskrivs skapa stressorer inom kulturskolelärarnas vardag. Resultatet visar på att vissa ramfaktoriella ram-, regel-, och målsystem skapar stressorer som i sin tur leder till bildandet av stress. Stressorerna som beskrivs uppstå kan bero på brist på förberedelse- eller planeringstid, arbetstider, organisatorisk volatilitet kring förutsättningar och riktlinjer, samt envägskommunikation från ledning. Dessa stressorer bidrar ibland till anpassningar som förebygger skapandet av nya stressorer men i vissa fall beskrivs stressorerna bidra till rekursiva stressorskapande processer i de fallen då kulturskolelärarna inte har någon möjlighet att påverka stressorerna i sig.
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