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1
Merlot, Elodie. "Modulation de la production de cytokines par l'environnement social et susceptibilité aux infections". Paris, Institut national d'agronomie de Paris Grignon, 2003. https://pastel.archives-ouvertes.fr/pastel-00000790.
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L'environnement social contribue au développement et à l'expression de maladies. En effet, dans les espèces sociales, la susceptibilité aux infections dépend de la position sociale mais les bases endocriniennes et immunitaires de ces différences au sein du groupe sont ignorées. De plus, une modification de la structure sociale engendre un stress important dont les conséquences immunitaires sont encore sujettes à controverse. Ce travail de thèse a pour objectifs (1) de décrire l'influence du statut social sur le fonctionnement des systèmes endocrinien et immunitaire, (2) de préciser les effets du stress social sur la production de cytokines et la susceptibilité aux infections et (3) de rechercher des facteurs à l'origine de la variabilité des conséquences immunitaires du stress social. Une étude introductive sur le porcelet mise à part, un modèle murin a été utilisé. Les résultats montrent une influence du statut social. En absence de stress, les dominants présentent des niveaux de base de corticostérone et une réponse à la tuberculine supérieurs aux dominés. Suite à une procédure de défaite sociale chronique, les dominants sont plus affectés que les dominés. La défaite sociale accroît la réactivité inflammatoire mais ne modifie pas l'équilibre de la production de cytokines de type1 et 2 et n'affecte pas la réponse à une infection mycobactérienne. Les conséquences immunitaires de la défaite sociale ne sont observées que lorsque le stress est associé à des combats et à des blessures. Ces travaux montrent enfin que la réponse au stress dépend de l'histoire sociale de l'individu, en particulier de son statut social, et son histoire immunitaire récenteIn social species, social environment contributes to the development and expression of diseases. Indeed, the social position in a group modulates susceptibility to infections. However, the endocrine and immune mechanisms involved in these differences are not known. Furthermore, instability in the social organisation generates a severe stress of which immune consequences are still controversial. The purposes of this thesis are (1) to describe the influence of social status on the endocrine and immune systems, (2) to specify the effects of social stress on cytokine production and susceptibility to infections and (3) to look for possible sources of variability in the immune consequences of social stress. Excepted a single study on piglets, experiments were performed in mice. Results show an influence of social status. In the absence of stress, dominants show higher basal corticosterone levels and specific response to tuberculin than subordinates. After social defeat, dominants are more affected. Social defeat increases inflammatory reactivity but does not clearly modify the balance between Th1 and Th2 cytokines production and does not affect the development of specific immunity against a mycobacterial infection. Immune effects of social defeat can be observed only when the stress involves significant fights and injuries. Our work also shows that the response to stress depends on individual social experience, in particular on social status, and on the recent immune experience of the individual
2
Blein, Sophie. "Étude de la variabilité du génome mitochondrial comme facteur de susceptibilité au cancer du sein". Thesis, Lyon 1, 2014. http://www.theses.fr/2014LYO10240/document.
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Une large part de la composante génétique du risque de cancer du sein est encore inexpliquée. J'ai ainsi étudié dans quelle mesure les variants observés sur le génome mitochondrial pourraient en partie expliquer ce risque. En effet la mitochondrie, en tant que source d'énergie cellulaire, est un organite impliqué dans la synthèse des espèces oxygénées réactives ou radicaux libres, éléments contribuant à l'instabilité génomique et au développement tumoral. Un premier axe de recherche m'a conduit à étudier une interaction potentielle entre des variants du génome mitochondrial et du génome nucléaire, en conjonction avec la consommation d'alcool. J'ai ensuite analysé les haplogroupes mitochondriaux peuvent être considérés en tant que potentiels modificateurs de l'association entre le risque de cancer du sein et les mutations causales portées par les gènes BRCA1 et BRCA2. L'haplogroupe T1a1 a été identifié comme modificateur du risque conféré par les mutations pathogènes localisées sur le gène BRCA2. Enfin, j'ai caractérisé par séquençage à haut débit le génome mitochondrial de 436 femmes ayant un cancer du sein et de forts antécédents familiaux, mais n'étant porteuses d'aucune mutation causale sur BRCA1 et BRCA2. Plusieurs variants ont été prédits comme dommageables. Deux gènes en particulier MT-ATP6 et MT-CYB, sont spécifiquement enrichis à la fois en nombre de variants portés, et de par le nombre d'individus porteurs de ces variants dans notre étude. L'ensemble du travail réalisé a ainsi contribué à enrichir les connaissances sur les potentielles associations entre les variations du génome mitochondrial et le risque du cancer du seinA large part of the genetic component of breast cancer risk (BCR) is still unexplained. Therefore I studied if variants of the mitochondrial genome (mtDNA) might explain a part of this risk. In fact, mitochondria is the main source of reactive oxygen species (ROS), which contribute to genomic instability and tumor development. As a first axis of research, I studied potential interactions between some nuclear and mitochondrial variants, in conjugation to alcohol consumption. Despite the large dimensions of our dataset, the lack of statistical significant interaction in our data might reveal that former published results that show such interactions were not robust. I also studied if mitochondrial haplogroups could be considered as modificators of known association between BCR and pathogenic mutations in the BRCA1/2 genes. I identified haplogroup T1a1 such as modificator for individuals carrying a mutated BRCA2. Finally, I characterized by NGS mitochondrial genome of women diagnosed for a familial breast cancer, but tested negative for known pathogenic BRCA1/2 mutations. Several variants were identified as potentially damaging. Two genes, MT-ATP6 and MT-CYB are specifically enriched both in terms of distinct variants and in the number of individuals carrying these variants. They are both essential structural components of the mitochondrial respiratory chain, the main ROS production source in the cell. All these analyses contribute to enrich the knowledge about associations between BCR and variability of mtDNA, by integrating questions linked to interactions between genomic variants, environmental exposure, and effect modifications related to mitochondrial haplogroups
3
Rakotobé, Malalaniaina. "Bases neuro-développementales de la susceptibilité à l’anxiété : apports de l’étude du système habénulo-interpédonculaire". Electronic Thesis or Diss., Université Côte d'Azur, 2021. http://www.theses.fr/2021COAZ6002.
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Les circuits de récompense du cerveau sont des réseaux neuronaux qui modulent positivement ou négativement la motivation à agir. Ils sont essentiels à la survie en sélectionnant les comportements adaptés à la situation, comme fuir les dangers ou rechercher de la nourriture. Leurs dysfonctionnements peuvent entraîner des troubles de l’humeur et des addictions. Bien que ces troubles psychiatriques se manifestent chez l’adulte, selon l’hypothèse neuro-développementale ils peuvent avoir une origine plus précoce. En effet, il existe des périodes particulières du développement appelées périodes critiques, durant lesquelles les facteurs génétiques et environnementaux influencent la maturation des circuits neuronaux. Un environnement stressant et/ou un défaut d’expression de gènes développementaux durant ces périodes, peuvent conduire à la malformation de ces circuits neuronaux, dont le système de récompense, et ainsi créer une prédisposition à des maladies psychiatriques. Le système habénulo-interpédonculaire (HIPS), constitué de l’habénula médiane (MHb) et de sa principale cible, le noyau interpédonculaire (IPN), émerge comme un composant clé de ce système de récompense. Il est impliqué dans des pathologies comme l’addiction, l’anxiété et la dépression. Notre équipe a récemment montré que le facteur de transcription Otx2 est essentiel pour la formation du HIPS. Son expression est maintenue dans le HIPS tout au long de la vie, fortement dans les derniers neurones générés dans la MHb (neurones Otx2High) et dans les sous-noyaux latéraux et le sous-noyau central de l’IPN caudal, suggérant qu’il pourrait aussi jouer un rôle dans la maturation et le fonctionnement du HIPS. Dans l’aire tegmentale ventrale (VTA), un autre acteur du système de récompense, un stress chronique subi pendant l’enfance diminue le niveau d’expression d’Otx2 et prédispose à la dépression et à l’anxiété. Otx2 pourrait jouer un rôle similaire dans la réponse du HIPS au stress pendant des périodes critiques du développement. Ce travail de thèse vise à mieux comprendre comment des facteurs génétiques et environnementaux affectant le développement du HIPS peuvent conduire à l’apparition de troubles psychiatriques. La première partie de la thèse montre que les neurones Otx2High de la MHb projettent sur les neurones Otx2+ de l’IPN, révélant l’existence d’un sous-circuit Otx2 dépendant dans le HIPS. L’activation chémo-génétique de la MHb à l’aide d’un DREADD a confirmé que les neurones Otx2High de la MHb sont capables de moduler l’activité des neurones Otx2+ de l’IPN et démontre qu’ils forment un sous-circuit au sein du HIPS, marqué par l’expression d’Otx2 et dénommé HIPOPS (Habenulo-InterPeduncular-Otx2-Positive-System).Dans la deuxième partie de ce projet, la période critique du développement du HIPS sensible au stress a été recherchée. L’utilisation des marqueurs d’activation neuronale Fos et Egr1 a permis d’identifier une période préadolescente durant laquelle le HIPS est plus réactif à un stress chronique. De manière intéressante, ce stress chronique engage particulièrement l’activité du HIPOPS, soulignant l’implication de ce sous-circuit dans la réponse au stress. Dans la troisième partie, un modèle de stress chronique « à deux coups » a été développé, et révèle que ce stress chronique subi durant la préadolescente prédispose à l’anxiété mais pas à la dépression à long-terme. Dans une dernière partie, les effets d’une délétion conditionnelle d’Otx2 dans le HIPS sur ces comportements ont été étudiés. Cette étude a permis de montrer que la délétion d’Otx2 dans la MHb protège des effets délétères du stress chronique préadolescente sur l’anxiété. Donc, l’interaction entre environnement (le stress) et gènes (Otx2) à la préadolescence détermine la susceptibilité à développer une anxiété chronique à long-terme et qu’un des supports cellulaires de cette susceptibilité est le HIPOPS, un circuit logé au cœur du HIPS, identifié par l’expression d’Otx2Reward circuits of the brain are neuronal networks that modulate positively or negatively the motivation to act according to the situation. They are essential for the survival of the subject and of species by selecting the appropriate behaviors, such as fleeing the danger or searching for food. Dysfunctions of these circuits can lead to mood disorders and addictions. Although these psychiatric disorders can emerge in adulthood, according to the neurodevelopmental hypothesis they can find their origins at a much earlier stage. Indeed, there are periods of development, called critical periods of development, during which genetic and environmental factors influence the maturation of neuronal circuits. A stressful environment and/or defaults in the expression of developmental genes during these critical periods can lead to the malformation of neuronal circuits, including the reward circuits, creating a predisposition to psychiatric disorders. The habenulo-interpeduncular system (HIPS), composed of the medial habenula (MHb) and its main target, the interpeduncular nucleus (IPN), emerges as a key component of the reward circuits. It is notably involved in disorders such as addiction, anxiety and depression. Our team has recently identified the Otx2 transcription factor as an essential genetic factor for the formation of the MHb and IPN. Otx2 expression is maintained in the HIPS throughout life, strongly in the last neurons generated in the MHb (Otx2High neurons) and in neurons of the lateral and central subnucleus of the caudal IPN, suggesting that it might also play a role in the maturation and functioning of the HIPS. We already know that in the ventral tegmental area (VTA), another actor of the reward circuits, a chronic stress, endured during a specific period of childhood decreases the expression level of Otx2 and predisposes to depression and anxiety. It is thus possible that Otx2 might play a similar function in the HIPS response to stress during periods of development. This thesis work aimed to better understand how genetic and environmental factors affecting the development of the HIPS could lead to the development of psychiatric disorders.The first part of this thesis shows that Otx2High neurons of the MHb project on the Otx2+ neurons of the IPN, revealing an Otx2-dependant sub-circuit in the HIPS. The MHb was then chemogenetically activated with the use of DREADD to verify that Otx2High neurons of the MHb are indeed able to modulate the activity of the Otx2+ neurons of the IPN and confirmed the idea that these neurons constitute a sub-circuit of the HIPS, labelled with the expression of Otx2, that we will call the HIPOPS (Habenulo-InterPeduncular-Otx2-Positive-System).In the second part of this project, a critical period of development during which the HIPS is more sensitive to stress has been searched. By using Fos and Egr1, two neuronal markers of activity, we identified a preadolescent period during which the HIPS is more responsive to chronic stress. Interestingly, that chronic stress involves more particularly the activity of the HIPOPS, emphasizing the implication of that sub-circuit in the stress response.In the third part, a “2-hit” stress protocol of chronic stress has been developed and revealed that a chronic stress endured during preadolescence predisposes to anxiety but not to depression in the long-term. In the last part, the effects of Otx2 conditional deletion in the HIPS has been assessed. This study shows that Otx2 deletion in the MHb protects from the deleterious effects of preadolescent chronic stress on anxiety symptoms. This work, therefore, demonstrates that the interaction between environment (stress) and genes (Otx2) during preadolescence determines the susceptibility to develop chronic anxiety in the long term and that one of the cellular support of that susceptibility is the HIPOPS, a circuit lodged inside the HIPS, recognizable by Otx2 expression
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Moulin, Sophie. "Rôle de l'hypoxia-inducible factor-1 dans la susceptibilité myocardique à l'ischémie-reperfusion induite par l'hypoxie intermittente". Thesis, Université Grenoble Alpes (ComUE), 2018. http://www.theses.fr/2018GREAV034/document.
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Le syndrome d’apnées obstructives du sommeil (SAOS) est un problème de santé publique majeur qui est considéré comme un facteur indépendant de risque de survenue d’un infarctus du myocarde (IM). Les altérations cardiovasculaires associées au SAOS sont principalement dues à l’hypoxie intermittente (HI) chronique. En particulier, l’HI induit l’activation du facteur de transcription hypoxia-inducible factor-1 (HIF-1), susceptible d’être impliqué dans la vulnérabilité accrue du myocarde à l’ischémie-reperfusion. L’objectif de cette thèse était d’étudier le rôle de HIF-1 dans les mécanismes induits par l’HI et impliqués dans l’augmentation de la taille de l’infarctus suite à une ischémie-reperfusion. Ces travaux ont mis en évidence deux nouveaux effets délétères de l’HI, à savoir l’induction d’un stress du réticulum endoplasmique (RE) et d’altérations mitochondriales. A travers, l’inhibition génétique et/ou pharmacologique de HIF-1, nous avons montré que HIF-1 apparaît comme un acteur primordial dans l’ensemble des mécanismes délétères de l’HI, incluant ceux découverts lors de cette thèse. De plus, HIF-1 joue un rôle majeur dans l’augmentation de la taille de l’IM induite par l’HI chronique. Parallèlement, son activation myocardique est corrélée à l’index d’apnées-hypopnées chez des patients apnéiques atteints d’une maladie coronarienne (comparativement aux non-apnéiques). Par conséquent, l’activation de HIF-1 pourrait être utilisée comme marqueur diagnostic du SAOS chez les patients à risque cardiovasculaire. HIF-1 pourrait également représenter une cible pour le développement de nouvelles thérapies complémentaires ou substitutives aux traitements actuelsObstructive sleep apnea syndrome (OSAS) is a major public health problem that is considered an independent risk factor for the occurrence of myocardial infarction (MI). The cardiovascular alterations associated with OSA are mainly due to the chronic intermittent hypoxia (IH). In particular, activation by IH, the hypoxia-inducible factor-1 (HIF-1) transcription factor likely contributes to enhance myocardial vulnerability to ischemia-reperfusion injury. The aim of this thesis was to study the role of HIF-1 in the mechanisms involved in the increase in MI induced by chronic IH. This work has highlighted two new deleterious consequences of IH exposure, namely endoplasmic reticulum (ER) stress and mitochondrial alterations. Through genetic and/or pharmacological inhibition of HIF-1, we have shown that HIF-1 appears to be a primordial actor in all the deleterious mechanisms of IH, including those discovered during this thesis. HIF-1 also appears to play a major role in the IH-induced increase in MI size. In parallel, its myocardial activation is correlated with the apnea-hypopnea index in apnoeic, compared to non-apnoeic, patients with coronary heart disease. Therefore, HIF-1 activation could serve as a diagnostic marker of OSA in patients with cardiovascular risk. HIF 1 could also be a target for new therapeutic approaches, in complement or replacement of standard treatments
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Le, guernic Antoine. "Effets sublétaux d'une contamination métallique liée à des rejets miniers uranifères sur l'épinoche à trois épines (Gasterosteus aculeatus L.). Implication dans la susceptibilité envers un stress biologique". Thesis, Reims, 2015. http://www.theses.fr/2015REIMS027.
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L’extraction de l’uranium a eu pour conséquence une remobilisation de cet actinide au niveau des écosystèmes avoisinants les mines. L’utilisation de sels métalliques lors de la réhabilitation des sites miniers et la présence naturelle de métaux ont accentué les niveaux de la contamination métallique dans les hydrosystèmes soumis aux rejets miniers uranifères.Des expériences in situ ont été conduites au niveau de deux anciens sites miniers uranifères français. L’encagement de l’épinoche à trois épines a été employé pour connaître les effets sublétaux de ce mélange métallique, ainsi que sur la susceptibilité de ce poisson envers un stress biologique.Cette pollution, caractérisée par de plus importantes concentrations métalliques (notamment en uranium), a entraîné un stress oxydant chez l’épinoche visible sur plusieurs biomarqueurs, ainsi que d’autres effets dépendants du site d’exposition.La contamination polymétallique a occasionné une augmentation de la susceptibilité des épinoches au stress biologique, en empêchant leurs réponses phagocytaire antioxydante à ce stress. Ces travaux ont permis de renforcer l’intérêt de la technique d’encagement lors d’une étude environnementale, et celui des immunomarqueurs au sein d’une approche multi-biomarqueursUranium extraction has resulted in a remobilisation of this actinide into mine surrounding ecosystems. Uses of metal salts during mining site rehabilitation, and the natural presence of metals have increased the metal contamination in hydrosystems submitted to mine tailings.In situ experiments were conducted in two former French uranium mining sites. Three-spined stickleback caging was used to determine the sublethal effects of this metal mixture on this freshwater fish, as well as its effects on fish susceptibility to a sudden biological stress.This pollution, characterised by higher metal concentrations (especially for uranium), has led to an oxidative stress in sticklebacks visible through several biomarkers, and other effects dependent on the study site. The polymetallic contamination has modified the stickleback responses to the biological stress, by preventing their phagocytic and antioxidant responses. This work has reinforced the interest of the caging technique during environmental studies and that of immunomarkers in a multi-biomarker approach
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Pujol, Marine. "Variabilité comportementale en réponse au stress social : influence du variant allélique VGLUT3-p.T8I sur l'acétylcholine et la dopamine dans le noyau accumbens". Electronic Thesis or Diss., Sorbonne université, 2024. http://www.theses.fr/2024SORUS098.
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Le stress représente un facteur de risque majeur dans le développement des troubles psychiatriques et des troubles du sommeil. La diversité des réponses émotionnelles au stress résulte de l'influence conjointe de facteurs environnementaux et génétiques. Le noyau accumbens (NAc) joue un rôle central dans la susceptibilité au stress et récemment, son implication dans la régulation du sommeil a été mise en évidence. Les adaptations comportementales liées à la résilience ou la susceptibilité au stress sont modulées par les transmissions dopaminergique et cholinergique au sein du NAc. L'acétylcholine (ACh) provient principalement des interneurones cholinergiques (CINs), qui communiquent à la fois avec du glutamate (Glut) et de l'ACh, respectivement grâce au transporteur vésiculaire du glutamate de type 3 (VGLUT3) et au transporteur vésiculaire d'acétylcholine (VAChT). L'équipe a récemment montré que le variant allélique p.T8I-VGLUT3 entraine une diminution de la transmission cholinergique dans le striatum, sans affecter le transport du Glut. Ainsi, l'objectif de ma thèse a été de caractériser le rôle du variant allélique p.T8I dans la réponse au stress en caractérisant le comportement et le sommeil ainsi que les transmissions d'ACh et de DA associées dans le NAc d'un modèle murin. Pour cela, j'ai évalué le comportement social, de type anxieux et dépressif, ainsi que les cycles veille-sommeil des souris VGLUT3T8I/T8I et témoins mâles et femelles avant et après un stress chronique de défaite sociale (CSDS). Afin d'étudier le rôle de l'ACh et de la DA dans ces comportements, j'ai enregistré leur dynamique de libération par photométrie de fibre à l'aide de biosenseurs fluorescents dans ce modèle murin.Les données obtenues montrent que le variant p.T8I est associé à un évitement social accru dépendant de la cible sociale, et de niveaux élevés d'anxiété, accompagnés d'une architecture du sommeil distincte en réaction au stress. De plus, ces comportements sont corrélés à une libération réduite d'ACh en réponse au stress chez les mâles. Ces travaux permettent ainsi de mettre en évidence la relation entre le variant p.T8I, les transmissions d'ACh et de DA, et la réponse au stress chronique social, impliquée dans la susceptibilité au stressStress is a risk factor for the development of psychiatric conditions such as generalized anxiety and major depressive disorder which are often associated with sleep disturbances. The behavioral adaptation to stress is influenced by a combination of environmental and genetic factors, leading to significant variability among individuals. The nucleus accumbens (NAc) plays a critical role in stress susceptibility and sleep regulation. In the NAc, the behavioral adaptations associated with resilience or susceptibility to stress are modulated by dopamine (DA) and acetylcholine (ACh) signals. The latter is predominantly released by cholinergic interneurons (CINs). Notably, CINs have the ability to signal with both ACh and glutamate through the expression of vesicular acetylcholine transporter (VAChT) and vesicular glutamate transporter 3 (VGLUT3). Our lab recently showed that the VGLUT3-p.T8I allelic variant results in a reduced ACh release from CINs without affecting glutamate release.The objective of my PhD was to elucidate the role of the p.T8I variant in shaping behavioral and sleep responses to stress as well as the stress-associated neuronal ACh and DA dynamics in the NAc. To address these questions, I took advantage of a mouse line carrying the p.T8I variant (VGLUT3T8I/T8I) to study social, anxiety- and depressive-like behaviors as well as sleep-wake patterns in male and female mice both before and after chronic social defeat stress (CSDS) exposure. Then, I measured in vivo ACh and DA dynamics in the NAc using fiber photometry coupled with fluorescent biosensors to assess their release in response to stress. The findings indicate that the p.T8I variant is associated with enhanced social cue discrimination characterized by high target-dependent social avoidance, and elevated anxiety-like levels, accompanied by distinct acute stress-induced sleep changes. Moreover, these behaviors are associated with reduced stress-induced ACh release in the NAc in male mice. Together, these findings reveal the intricate relationship between the p.T8I variant, diminished cholinergic transmission within the NAc and susceptibility to stress
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Etain, Bruno. "Contribution à l'étude des facteurs génétiques et environnementaux de susceptibilité aux troubles bipolaires : études du trouble bipolaire à début précoce et des traumatismes affectifs de l’enfance". Thesis, Paris Est, 2009. http://www.theses.fr/2009PEST0048.
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Les troubles bipolaires (TB) sont des maladies psychiatriques dont le déterminisme complexe fait intervenir des facteurs génétiques et environnementaux de susceptibilité. Les efforts d’identification des facteurs génétiques ont produit des résultats discordants et les facteurs environnementaux restent mal connus. Notre équipe a contribué à identifier une forme à début précoce des TB (TB-DP), son caractère fortement familial en faisant un candidat pour faciliter l’identification de gènes de susceptibilité. Ainsi, nous avons réalisé un criblage systématique du génome dans le TB-DP suggérant une liaison avec les régions chromosomiques 2p21, 2q14, 3p14, 5q33, 7q36, 10q23, 16q23 et 20p12. Nous avons montré des associations entre le TB-DP et le gène SNAP25 (rôle dans les mécanismes d’exocytose, région 20p12) et entre les TB et le gène codant l’ASMT (rôle dans la synthèse de la mélatonine). Enfin, une étude d’association pangénomique suggère une association entre le TB-DP et deux gènes de la voie du phosphatidyl-inositol (PLEKHA5 et PLCXD3). Concernant les facteurs environnementaux, les traumatismes affectifs subis dans l’enfance (principalement les abus émotionnels) sont associés aux TB, influencent deux dimensions constitutives des TB (labilité affective et intensité des affects) et interagissent avec le 5HTTLPR pour moduler l’âge de début des troubles. Ces travaux illustrent la pertinence de se focaliser sur le TB-DP pour identifier des gènes de susceptibilité, la nécessité d’explorer plus finement les facteurs environnementaux (notamment les stress précoces) et de considérer les interactions gène-environnement afin de mieux appréhender le déterminisme complexe des TBBipolar disorders (BD) are psychiatric diseases with a complex determinism in which genetic and environmental susceptibility factors are involved. Attempts to identify genetic factors have produced conflicting results and environmental factors remain unknown. Early-onset bipolar disorder (EO-BD) is a clinical entity that is characterized by a strong familial aggregation ; a specific focus on this subtype might facilitate the identification of susceptibility genes. A genome-wide scan in EO-BD has suggested eight regions of linkage (chromosomal regions 2p21, 2q14, 3p14, 5q33, 7q36, 10q23, 16q23 and 20p12). We have demonstrated an association between EO-BD and the SNAP25 gene (located at 20p12 and involved in exocytosis). We have demonstrated an association between BD and the ASMT gene (involved in the synthesis of melatonin). Finally, a genome-wide association study has suggested the involvement of two phosphatidyl-inositol pathway related genes in the susceptibility to EO-BD (PLEKHA5 et PLCXD3). Concerning environmental susceptibility factors, childhood affective traumatic events (mainly emotional abuse) are associated with BD, might influence two core dimensions of BD (affective lability and affect intensity) and might interact with the serotonin transporter genelinked polymorphic region to modulate the age of onset of the disorder. These studies illustrate the relevance of focusing on the early onset subgroup of the disease to identify susceptibility genes, the need to further explore early stressors as environmental factors associated with BD and to investigate the complex relationships between these two kinds of susceptibility factors
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Jones, C. A. "A study of stress susceptibility in pigs". Thesis, University of Bristol, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.372043.
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Thomas, Gladys Ruth. "Susceptibility of Brugia malayi to oxidative and nitrosative stress". Thesis, Imperial College London, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.267808.
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鍾慧虹 e Wai-hung Angela Chung. "Cognitive vulnerability, stress, and postpartum depressive symptomatology: a prospective study in HongKong". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2006. http://hub.hku.hk/bib/B37101055.
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Shushan, S. M. "The susceptibility of diffusion bonded joints to stress corrosion cracking". Thesis, University of Newcastle Upon Tyne, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.295046.
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Chung, Wai-hung Angela. "Cognitive vulnerability, stress, and postpartum depressive symptomatology a prospective study in Hong Kong /". Click to view E-thesis via HKUTO, 2006. http://sunzi.lib.hku.hk/hkuto/record/B37101055.
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Lorho, Nina. "Stress corrosion cracking susceptibility in Alloy 600 with different strain histories". Thesis, University of Manchester, 2014. https://www.research.manchester.ac.uk/portal/en/theses/stress-corrosion-cracking-susceptibility-in-alloy-600-with-different-strain-histories(59eabd1d-b254-48bc-afca-e979f5d4e6c2).html.
Texto completo da fonteResumo:
Lifetime prediction of components in Alloy 600 is a major concern for nuclear power plants. Alloy 600 components have been shown to be susceptible to stress corrosion cracking (SCC). In the 1990’s, an engineering model was developed in order to predict the life time as a function of the main macroscopic parameters (stress, environment, material), based on laboratory results. This model has since been used to predict the ranking of various Alloy 600 components, using the knowledges of the manufacturing and service conditions for each component. It was applied successfully in the case of forged control rod drive mechanism (CRDM) nozzles. However, it was found necessary to improve this model to account for the strain history of the different components. Predictions using the model, investigated from an array of test results on Alloy 600 in laboratory primary water, have demonstrated that the time for initiation differed significantly according to the strain path applied to the specimen. The present work is dedicated to assess SCC results from samples with different strain paths and different level of cold work in order to better understand the manufacturing conditions on SCC. The samples are machined in three different directions and tested at different durations in order to model the time for transition (transition between slow and fast propagation) as a function of cold work, strain path and stress. Thermomechanical treatments are also applied on two different heats of Alloy 600: forged WF675 (very susceptible to SCC in as received conditions) and rolled 78456/337 (non susceptible to SCC in as-received conditions) in order to transform the forged microstructure into a microstructure close to the rolled microstructure and vice-versa. These microstructures are then tested in primary conditions and the results are compared to the results obtained on as-received material in order to get a better understanding of manufacturing process and microstructure parameters regarding SCC behaviour.
14
Sivathayalan, Sivapathasundaram. "Fabric, initial state and stress path effects on liquefaction susceptibility of sands". Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape4/PQDD_0017/NQ56623.pdf.
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Anyanwu, Ezechukwu John. "Low Alloy Steel Susceptibility to Stress Corrosion Cracking in Hydraulic Fracturing Environment". University of Dayton / OhioLINK, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=dayton1398948610.
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Strader, Katherine C. "Phase Transformation Behavior and Stress Relief Cracking Susceptibility in Creep Resistant Steels". The Ohio State University, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=osu1408973568.
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17
Rozentals, Emils. "Email load and stress impact on susceptibility to phishing and scam emails". Thesis, Luleå tekniska universitet, Digitala tjänster och system, 2021. http://urn.kb.se/resolve?urn=urn:nbn:se:ltu:diva-85403.
Texto completo da fonteResumo:
How does the email load and stress affect the susceptibility to phishing and scam emails? The study was conducted with a Qualitative research approach. Semi-structured interviews were selected for the data gathering. Thematic Analysis was used to analyze Empirical data. This research studied if a high email load affects the likelihood of falling victim to phishing and scam attacks. Research was studied through a theoretical lens of stress, since high email load is subjective for each individual and stress rate can show better how people are perceiving their email load. Findings suggest that high email load for the majority of people in this study, does increase the susceptibility towards phishing and scam emails. Furthermore, those people with higher email load who are processing their emails heuristically evaluated their stress rates higher than those with high email load who are processing their emails systematically. Therefore, the results indicate that there is a relation between high email load, stress and susceptibility to phishing and scam emails. In this study, it was found that majority of respondents described high stress as a factor that played a role in their susceptibility of falling victim to phishing and scam emails.
18
Pisu, Davide. "ROLE OF SigE IN M.TUBERCULOSIS DRUG SUSCEPTIBILITY AND PERSISTENCE". Doctoral thesis, Università degli studi di Padova, 2015. http://hdl.handle.net/11577/3424157.
Texto completo da fonteResumo:
M.tuberculosis (Mtb) is one of the most important pathogens that infect humans and it is the causative agent of tuberculosis (TB), a disease that dates back to ancient times.
The World Health Organization (WHO) estimates that more than one third of the total whole population is infected with Mtb and each year about 1,5 millions people die from tuberculosis.
Two of the main problems in M. tuberculosis control are the lengthy treatment and the enormous reservoir of latent carriers.
A common explanation for the need of lengthy treatment is that all or part of the population enters a non-replicating persistent state characterized by some degree of dormancy. These are called “dormant” or “persistent” cells. This phenomenon, whose physiology is not well known, is very important for the treatment of infections, given the fact that dormant cells are resistant to many drugs.
The aim of this study was to find new potential molecular targets that can be used to enhance the effectiveness of traditional antibacterial drugs, in order to develop new therapies effective against this population of non-replicating cells.
Sigma factors (σ) regulate gene expression by binding to the RNA polymerase core enzyme and they could be important targets of new therapeutic approaches in the future, as some evidences recently showed they may play an essential role during Mtb persistence.
In this work, we focused on one of these sigma factors, SigE, that was previously described to have a role in response to the different types of stresses bacteria encounter during infection, such as heat shock, surface and oxidative stresses (Manganelli et al., 2001).
Using a sigE null mutant and through a series of different molecular and phenotypic investigations, we demonstrated how SigE plays a crucial role in response to stresses caused by different classes of antimicrobials. Furthermore, we observed a strong decrease in persister cells production when the sigE mutant was exposed to high concentrations of antibiotics. Finally, we tested other sigma mutants, to investigate if such a feature was shared across sigma factors. Although we demonstrated sigB (which expression is controlled by sigE under stress conditions) involvement in persisters production, the vast majority of the features we described in this work were unique of the SigE sigma factor.
To conclude, with this work we were able to demonstrate how SigE may be a valid molecular target to develop new effective therapies against M.tuberculosis infections.M.tuberculosis (Mtb) è uno dei patogeni più importanti che infettano gli essere umani ed è l’agente eziologico della tubercolosi (TB), una malattia che risale a tempi antichi. L’Organizzazione Mondiale della Sanità (OMS) stima che più di un terzo dell’intera popolazione mondiale sia stata infettata da Mtb e che ogni anno circa 1,5 milioni di persone muoiano di tubercolosi. Due dei principali problemi nel controllo di questa malattia sono l’enorme serbatoio di portatori latenti e la lunghezza del trattamento terapeutico. Una spiegazione condivisa relativamente alla necessità di un trattamento terapeutico prolungato è che la totalità o una parte della popolazione batterica, nel corso di un’infezione, entri in uno stato non replicativo, caratterizzato da un certo grado di “dormienza”. Queste cellule quiescenti sono chiamate “persisters”. Questo fenomeno, la cui fisiologia non è ben nota, è molto importante per il trattamento delle infezione, in considerazione del fatto che le cellule dormienti sono tolleranti ad alte concentrazioni di molti farmaci e perciò non vengono da essi uccise. Lo scopo di questo studio è stato pertanto quello di trovare nuovi potenziali bersagli molecolari che possano essere utilizzati per migliorare l’efficacia dei trattamenti terapeutici tradizionali, al fine di sviluppare nuove terapie efficaci contro questa popolazione di cellule persistenti. I fattori sigma (σ) regolano l’espressione genica legandosi all’apoproteina polimerasica e, in futuro, potrebbero essere importanti bersagli molecolari di nuovi approcci terapeutici, in quanto alcuni recenti studi hanno dimostrato come essi potrebbero avere un ruolo chiave nel fenomeno della persistenza di M.tuberculosis. In questo lavoro ci siamo concentrati su uno di questi fattori sigma in particolare, SigE, che era stato descritto in precedenza nel giocare un ruolo di primaria importanza nella risposta ai diversi tipi di stress che Mtb incontra durante un’infezione, come shock termico, stress di superficie e ossidativo. (Manganelli et al., 2001). Utilizzando un mutante di delezione per sigE e, attraverso una serie di indagini molecolari e fenotipiche, siamo stati in grado di dimostrare come SigE rivesta un ruolo cruciale nella risposta ai diversi tipi di stress causati dall’esposizione a differenti classi di farmaci antibatterici. Inoltre, abbiamo osservato una forte riduzione nella produzione di cellule “persister” quando il mutante sigE è stato esposto ad elevate concentrazioni di farmaci antimicrobici. Infine, per verificare se queste caratteristiche fossero condivise tra i fattori sigma, abbiamo testato altri mutanti per differenti fattori sigma. Nonostante siamo stati in grado di dimostrare che anche sigB (la cui espressione è controllata da sigE in condizioni di stress) sia coinvolto nella produzione di cellule persistenti, tuttavia la maggior parte delle caratteristiche molecolari e fenotipiche che abbiamo descritto in questo lavoro sono attribuibili al solo fattore SigE. Per concludere, con questo lavoro siamo stati in grado di dimostrare come SigE possa essere un valido bersaglio molecolare per lo sviluppo di nuove terapie efficaci contro le infezioni causate da M.tuberculosis.
19
Smith, Vincent Peter. "The cuticular membranes of parasitic nematodes : structure, composition and susceptibility to oxidative stress". Thesis, Imperial College London, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.267287.
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Stenerud, Gaute. "The Susceptibility to Hydrogen Induced Stress Cracking for Alloy 718 and Alloy 725". Thesis, Norges teknisk-naturvitenskapelige universitet, Institutt for materialteknologi, 2014. http://urn.kb.se/resolve?urn=urn:nbn:no:ntnu:diva-26331.
Texto completo da fonteResumo:
The Hydrogen Induced Stress Cracking (HISC) susceptibility of Alloy 718 and Alloy 725 where examined and compared. Pre-charged samples of each alloy where stepwise loaded during polarization in Cortest Proof rings. A safe load was found from this stepwise loading. To confirm that these load levels were safe, pre-charged samples were loaded to this load for 30 days during cathodic polarization. After fracture the fracture surfaces were examined in scanning electron microscope and the hydrogen concentration were measured by hydrogen melt extraction. It was found that both alloy are severely embrittled by hydrogen. Both the ductility and stress at fracture were reduced by the same amount in both alloys. The constant load tests revealed a safe stress at 123,8 % of YS for Alloy 725 and 120,4 % of YS for Alloy 718. Based on this it was concluded that Alloy 725 is somewhat more resistant to HISC than Alloy 718.
21
Araujo, Alessandra M. "STRESS RESPONSES AND PACE OF LIFE PHENOTYPES PREDICT DISEASE SUSCEPTIBILITY AND HOST EPIZOOTIC POTENTIAL". OpenSIUC, 2015. https://opensiuc.lib.siu.edu/theses/1773.
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This thesis represents two lines of investigation that as a whole integrate physiology and ecology of infectious diseases. While each chapter is a distinct body of work, these studies are linked in that both focus on extrinsic or intrinsic factors influencing hosts’ susceptibility to infection, as well as hosts’ potential to transmit disease. In chapter one, I used a meta-analysis as a tool to review what is known about the stress-linked susceptibility hypothesis, which poses that persistent activation of the stress axis might result in increased disease susceptibility in wild animals, mainly as a result of allostatic overload and the immunosuppressive actions of stress hormones. My goal in evaluating the strength of association between distinct stressors and health indices in wildlife populations was manifold. First, I wanted to investigate which specific stressors are more likely to increase disease susceptibility in wild animals. Second, I was interested in the reliability of stress biomarkers as indicators of stress-induced immunosuppression or disease susceptibility. Finally, I used this chapter as a bridge for my second chapter by addressing how “fast-paced” and “slow-paced” phenotypes within wild populations cope differently with stressors, thus also differentially altering epizootic risk. My meta-analysis indicated that the highly variable outcomes of ecological studies can be attributed to several factors, ranging from possible erroneous classification of stimuli as physiological stressors to a lack of consensus on the endocrine profiles of stressed animals. The second chapter of this work consists of an empirical investigation of the pace-of-life (POL) hypothesis in the context of host disease susceptibility and transmissibility. Individuals with a fast-paced life history often exhibit relatively high metabolic rates and investment in growth, development, and reproduction. To support these faster rates, they often exhibit decreased investment in immunity, as well as associated bold behaviors for increased foraging and competiveness to ensure access to resources. These associated functional physiological and behavioral traits likely also influence exposure and susceptibility to pathogens, and infectiousness; factors central to disease dynamics. Through transmission trials using ranavirus and larval amphibians as a model system, I found that repeatable latency-to-food profiles of larval hosts, which characterize a POL axis associated with development and metabolic rates, were predictive of individual susceptibility and infectiousness. Faster-paced larval amphibians had greater exposure to pathogens (contacts), higher risk of infection (susceptibility), and shed greater pathogen populations when infected. Through these findings, I argue that The POL framework can allow for a priori identification of individual hosts that are more likely to spread infectious disease and may provide insight into understanding and potentially managing disease outbreaks that threaten wildlife and humans alike.
22
Cullen, Alexis Elizabeth. "Increased stress susceptibility and hypothalamic-pituitary-adrenal axis dysfunction : early markers of psychosis vulnerability?" Thesis, King's College London (University of London), 2014. http://kclpure.kcl.ac.uk/portal/en/theses/increased-stress-susceptibility-and-hypothalamicpituitaryadrenal-axis-dysfunction(b602f1f0-1006-4491-a112-83d5156f8e13).html.
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Background: Individuals with psychosis are characterised by increased exposure and reactivity to psychosocial stressors and abnormal hypothalamic-pituitary-adrenal (HPA) axis function [i.e., elevated cortisol levels, a blunted cortisol awakening response (CAR), and pituitary volume abnormalities]. The extent to which these features are present among at-risk individuals, prior to illness onset, is currently unclear. Aims: To determine whether putatively at-risk children who present multiple antecedents of schizophrenia (ASz) or a family history of illness (FHx) show increased susceptibility to psychosocial stressors and HPA axis abnormalities relative to typically-developing (TD) children. An additional aim was to explore associations between these measures and neurocognitive function. Methods: ASz (n=35), FHx (n=25), and TD (n=44) children were identified at age 9-12 years using a novel community-screening procedure or as relatives of individuals with schizophrenia. Measures of psychosocial stress, salivary cortisol, pituitary volume, and neurocognitive function were obtained at age 11-14 years. Results: Relative to TD children, both ASz and FHx children reported greater exposure to psychosocial stressors and were more distressed by these exposures (d=0.55-1.02, p<0.05). Additionally, FHx children, but not ASz children, showed a blunted CAR compared to TD children (d=0.73, p=0.01), yet neither group were characterised by elevated diurnal cortisol levels or pituitary volume abnormalities. In exploratory analyses, more abnormal HPA axis function (i.e., higher diurnal cortisol levels and a more blunted CAR) was associated with greater neurocognitive deficits among FHx and ASz children, whilst experiences of psychosocial stress were associated with better neurocognitive performance.
23
Chen, Jinwei. "The effects of specimen geometry of susceptibility to stress corrosion cracking (SCC) of steels". Thesis, University of Newcastle Upon Tyne, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.270796.
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Coulthard, Jacob, Westley Ongtengco, Jacob Garst, Michelle Chandley, Hui Wang-Heaton e Gregory A. Ordway. "Oxidative Stress Susceptibility of Oligodendrocytes in Major Depressive Disorder is Widespread in the Brain". Digital Commons @ East Tennessee State University, 2018. https://dc.etsu.edu/asrf/2018/schedule/47.
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Over 10 million people are affected by major depressive disorder (MDD) in the U.S. annually. Unfortunately, about 1/3 of these people do not achieve adequate remission of symptoms with current antidepressant drugs. It is expected that an improved understanding of the pathobiology of depression will result in the development of more effective antidepressant treatments. Research by this lab in recent years has provided evidence of elevated DNA damage in brain white matter in MDD, discovered by studying brain tissues from human brain donors that had an active diagnosis of MDD at the time of death and age-matched control donors who had no psychiatric illness. Accompanying this DNA damage was an elevation of gene expression of DNA base excision repair enzymes in white matter oligodendrocytes, a major cell type in brain white matter. In addition, gene expression of antioxidant genes in these oligodendrocytes was significantly lower in MDD than in control donors, suggesting that these cells were especially susceptible to the damaging effects of oxidative stress in MDD. This initial data was generated by measuring gene expressions in oligodendrocytes captured from two specific regions of white matter in the brain, the frontal cortex, and amygdala. In the present study, we designed experiments to determine whether these effects are found in oligodendrocytes in other areas of the brain in MDD and to determine whether another cell type in the brain, neurons, are similarly affected. Towards these aims, oligodendrocytes from two other brain regions (occipital cortical white matter and brainstem locus coeruleus) were captured by laser microdissection from MDD and control donors. In addition, CA1 pyramidal neurons were captured from the anterior hippocampus of MDD and control donors. We chose to specifically study hippocampal CA1 pyramidal neurons because these neurons are normally sensitive to oxidative stress, and reasoned that these cells would be among brain neurons most likely affected by conditions of elevated oxidative stress in MDD. Approximately 500 cells were captured from each brain area using immunohistochemically-guided laser capture microdissection. RNA isolated from these cells was converted to cDNA by reverse transcription and subjected to quantitative polymerase chain reactions (PCR). Statistically significant reductions in antioxidant gene expression was observed in oligodendrocytes from MDD donors as compared to control donors regardless of the brain area from which the cells were captured. In contrast, no significant changes in antioxidant gene expression were observed in CA1 pyramidal neurons from MDD donors. Additionally in contrast to findings in oligodendrocytes, levels of gene expression of the DNA repair enzyme, poly(ADP-ribose) polymerase 1 (PARP1) in hippocampal CA1 pyramidal neurons from MDD donors was similar to that from control donors. These findings demonstrate that pathological DNA damage and repair mechanisms occur in brain oligodendrocytes throughout the brain, and similar mechanisms do not appear to affect hippocampal neurons. A better understanding of the cellular systems engaged by oxidative damage to oligodendrocytes in MDD has the potential to lead to the identification of unique targets for the development of novel antidepressant drugs.
25
Wodarcyk, John J. "Stress corrosion cracking susceptibility of AISI no. 1018 steel in low SO₂-CO₂-O₂ aqueous environments". Ohio : Ohio University, 1991. http://www.ohiolink.edu/etd/view.cgi?ohiou1183988473.
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26
Roberts, Susan. "The effect of dietary protein source on plasma parameters related to stress and behaviour in pigs varying in their susceptibility to stress /". Thesis, McGill University, 1992. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=56819.
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The present study was performed to determine if pigs varying in their susceptibility to stress, adapted to a casein-based diet, experience an improvement in biochemical parameters related to stress and behaviour compared to pigs adapted to the traditional western canadian cereal-based swine diet. Experiment 1 involved separating fifty-eight, 8-week old pigs according to genotype with respect to the halothane gene. Within each genotype pigs were divided into 2 groups and assigned to either a control diet or to a diet where most of the protein source was substituted for casein. All animals were adapted to diet for 6 weeks and experienced a weekly blood sampling stressor. Day 1, 14 and 35 of the plasma samples were analyzed for glucose, cortisol, ACTH, insulin, pyridoxal 5$ sp prime$-phosphate (PLP), amino acid concentrations and dopamine-$ beta$-hydroxylase (DBH) activity; metabolic indices known to be responsive to stress. Experiment 2 involved separating fifty-seven, 14-week old pigs in the same manner, then adapting the pigs to their respective diets for a period of 4 weeks. Afterwards, pigs were transferred from their pen to a novel pen-maze situation where they had their behaviour monitored for a period of one hour. Results of these experiments have revealed that (1) the stress susceptible and carrier pigs experienced reduced day 35 plasma glucose, PLP concentrations and DBH activity compared to normal pigs; (2) dietary adaptation to the casein diet resulted in greater day 14 and 35 PLP levels and day 35 essential amino acid lysine, threonine, methionine, tryptophan and arginine concentrations compared to control-adapted pigs; (3) the carrier pigs investigated their surroundings more frequently than the stress susceptible pigs, and the normal pigs engaged in the through-maze behaviour more often than the stress susceptible pigs; and (4) adaptation to the casein diet, compared to the control diet, resulted in fewer displacement-type behaviours such as drinking
27
Leech, Alexandra. "Struggling with susceptibility and stress : an exploration and expansion of vulnerability-stress models of depression and the potential for intervention in late adolescence". Thesis, University of Cambridge, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.608286.
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28
Skjönsberg, Åsa. "Hereditary susceptibility to inner ear stress agents studied in heterozygotes of the German waltzing guinea pig /". Stockholm, 2006. http://diss.kib.ki.se/2006/91-7140-817-7/.
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29
Wodarcyk, John J. Jr. "Stress corrosion cracking susceptibility of AISI No. 1018 steel in low SO 2CO 2O 2aqueous environments". Ohio University / OhioLINK, 1991. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1183988473.
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30
Sherwood, Patrick William. "Biochemical Mechanisms of Resistance and Susceptibility in the Pinus nigra - Diplodia sapinea Pathosystem". The Ohio State University, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=osu1408640310.
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31
Garry, Michael R. "Differential response and susceptibility to oxidative stress in mouse lung fibroblasts heterozygous for phospholipid hydroperoxide glutathione peroxidase (GPx4) /". Thesis, Connect to this title online; UW restricted, 2006. http://hdl.handle.net/1773/8465.
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32
Beal, Irina. "Event Sedimentology and Hydrodynamic Hindcasting of Storm Surge Deposits: Hurricane Sandy, New Jersey". Master's thesis, Temple University Libraries, 2014. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/281770.
Texto completo da fonteResumo:
GeologyM.S.
The impact of Hurricane Sandy (October 2012) on the Atlantic Coast of the United States resulted in massive overtopping (aggradation) of coastal barriers, along with localized overwash and breaching. A combination of high-frequency ground-penetrating radar (800 MHz GPR), low-field magnetic susceptibility (MS), and textural and mineralogical analyses was used to reconstruct the sedimentological and hydrodynamic parameters of the storm surge at two New Jersey sites immediately north of hurricane landfall: 1) Mantoloking and 2) Island Beach State Park (IBSP). Mantoloking represents a developed, scour-channelized backdune area with a 30-60 cm thick deposit consisting of 20-23 event horizons. Geophysical images reveal gently landward-dipping reflections. In contrast, IBSP site is a broad (width: 40 m) vegetated dune swale. GPR transects show landward-dipping tangential-oblique reflections as well as a conformable channel cut-and-fill structure (width: 7 m; depth: 1.5 m), producing a 0.7-1.5-m-thick deposit with 24-30 horizons. Within each sand-dominated event horizon, an upward 5-15% increase in mean grain size and 80-100% decrease in MS highlight the importance of hydrodynamic equivalency in lithological segregation within mixed-density fractions. Basal sub-layers enriched in heavy minerals (magnetite, ilmenite, garnet) yield MS of 100-350 μSI, in contrast to <40 μSI in quartz-rich upper sub-layers and pre-storm deposits. Several peaks in MS values correspond to an up to 65% increase in threshold shear stresses associated with individual unidirectional surge flows, with several most-enriched event horizons likely corresponding to waning-stage storm surge peaks recorded by offshore buoys. The sharp contact with the pre-storm surface produces distinct GPR reflections that allow accurate mapping of the thickness and extent of hurricane deposits. Together with potential correlation between lithological anomalies and high amplitude georadar signal return, the approach used in this study has applications to reconstructing event deposits in Quaternary sedimentary records. The new research findings have potential implications for reconstructing surge dynamics of recent hurricane events as well as quantitative hindcasting of hydrodynamic conditions responsible for lithologically diverse intervals in ancient tempestites.
Temple University--Theses
33
Beal, Irina. "Beal_Calculations.xls". Master's thesis, Temple University Libraries, 2014. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/281771.
Texto completo da fonteResumo:
GeologyM.S.
The impact of Hurricane Sandy (October 2012) on the Atlantic Coast of the United States resulted in massive overtopping (aggradation) of coastal barriers, along with localized overwash and breaching. A combination of high-frequency ground-penetrating radar (800 MHz GPR), low-field magnetic susceptibility (MS), and textural and mineralogical analyses was used to reconstruct the sedimentological and hydrodynamic parameters of the storm surge at two New Jersey sites immediately north of hurricane landfall: 1) Mantoloking and 2) Island Beach State Park (IBSP). Mantoloking represents a developed, scour-channelized backdune area with a 30-60 cm thick deposit consisting of 20-23 event horizons. Geophysical images reveal gently landward-dipping reflections. In contrast, IBSP site is a broad (width: 40 m) vegetated dune swale. GPR transects show landward-dipping tangential-oblique reflections as well as a conformable channel cut-and-fill structure (width: 7 m; depth: 1.5 m), producing a 0.7-1.5-m-thick deposit with 24-30 horizons. Within each sand-dominated event horizon, an upward 5-15% increase in mean grain size and 80-100% decrease in MS highlight the importance of hydrodynamic equivalency in lithological segregation within mixed-density fractions. Basal sub-layers enriched in heavy minerals (magnetite, ilmenite, garnet) yield MS of 100-350 μSI, in contrast to <40 μSI in quartz-rich upper sub-layers and pre-storm deposits. Several peaks in MS values correspond to an up to 65% increase in threshold shear stresses associated with individual unidirectional surge flows, with several most-enriched event horizons likely corresponding to waning-stage storm surge peaks recorded by offshore buoys. The sharp contact with the pre-storm surface produces distinct GPR reflections that allow accurate mapping of the thickness and extent of hurricane deposits. Together with potential correlation between lithological anomalies and high amplitude georadar signal return, the approach used in this study has applications to reconstructing event deposits in Quaternary sedimentary records. The new research findings have potential implications for reconstructing surge dynamics of recent hurricane events as well as quantitative hindcasting of hydrodynamic conditions responsible for lithologically diverse intervals in ancient tempestites.
Temple University--Theses
34
Beal, Irina. "Beal_CAMSIZERdata.xlsx". Master's thesis, Temple University Libraries, 2014. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/281772.
Texto completo da fonteResumo:
GeologyM.S.
The impact of Hurricane Sandy (October 2012) on the Atlantic Coast of the United States resulted in massive overtopping (aggradation) of coastal barriers, along with localized overwash and breaching. A combination of high-frequency ground-penetrating radar (800 MHz GPR), low-field magnetic susceptibility (MS), and textural and mineralogical analyses was used to reconstruct the sedimentological and hydrodynamic parameters of the storm surge at two New Jersey sites immediately north of hurricane landfall: 1) Mantoloking and 2) Island Beach State Park (IBSP). Mantoloking represents a developed, scour-channelized backdune area with a 30-60 cm thick deposit consisting of 20-23 event horizons. Geophysical images reveal gently landward-dipping reflections. In contrast, IBSP site is a broad (width: 40 m) vegetated dune swale. GPR transects show landward-dipping tangential-oblique reflections as well as a conformable channel cut-and-fill structure (width: 7 m; depth: 1.5 m), producing a 0.7-1.5-m-thick deposit with 24-30 horizons. Within each sand-dominated event horizon, an upward 5-15% increase in mean grain size and 80-100% decrease in MS highlight the importance of hydrodynamic equivalency in lithological segregation within mixed-density fractions. Basal sub-layers enriched in heavy minerals (magnetite, ilmenite, garnet) yield MS of 100-350 μSI, in contrast to <40 μSI in quartz-rich upper sub-layers and pre-storm deposits. Several peaks in MS values correspond to an up to 65% increase in threshold shear stresses associated with individual unidirectional surge flows, with several most-enriched event horizons likely corresponding to waning-stage storm surge peaks recorded by offshore buoys. The sharp contact with the pre-storm surface produces distinct GPR reflections that allow accurate mapping of the thickness and extent of hurricane deposits. Together with potential correlation between lithological anomalies and high amplitude georadar signal return, the approach used in this study has applications to reconstructing event deposits in Quaternary sedimentary records. The new research findings have potential implications for reconstructing surge dynamics of recent hurricane events as well as quantitative hindcasting of hydrodynamic conditions responsible for lithologically diverse intervals in ancient tempestites.
Temple University--Theses
35
Chen, Yuanneng. "Role of polymorphisms in genes affecting oxidative stress and immune response in susceptibility to alcoholic liver disease". Thesis, University of Newcastle Upon Tyne, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.391248.
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36
Sanchez, Camacho Lizeth J. ""Effect of AC interference on the corrosion cracking susceptibility of low carbon steel under cathodic protection."". University of Akron / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=akron1531157966071788.
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Ahmed, Ismaila Idowu. "The influence of material factors, including cold work, on the susceptibility of stainless steels to stress corrosion cracking". Thesis, University of Manchester, 2011. https://www.research.manchester.ac.uk/portal/en/theses/the-influence-of-material-factors-including-cold-work-on-the-susceptibility-of-stainless-steels-to-stress-corrosion-cracking(19937317-f1b4-4dbc-ab0e-3eab3760f716).html.
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The main objective of the thesis was to gain better understanding of key parameters associated with Cold Work (CW) and their possible effects on Stress Corrosion Cracking (SCC) susceptibility of Austenitic Stainless Steels (ASS) cold rolled to different degrees. The microstructural characterisation of the cold rolled ASS was carried out using optical microscopy to determine and correlate the average grain size with the level of CW. The assessment of martensite development during the CW was carried out using the neutron diffraction technique. The effects of CW levels and strain paths on the lattice strain evolution during the in-situ loading and on the mechanical failure of cold worked ASS were studied. The electrochemical behaviour of cold rolled ASS was also studied. Finally, The SCC susceptibility of ASS was investigated using the Slow Strain Rate Testing (SSRT) techniques. The post-mortem analyses of the failed samples were carried using the optical and Scanning Electron Microscopy (SEM). The study showed that the average grain size decreases with CW and reaches minimum at 20%CW. The smallest and the largest grain size occurred consistently on the Longitudinal (L) and Short-transverse (S) plane respectively. Evidence of martensite development was only found during the plastic deformation at cryogenic temperature and none was observed at ambient temperature. The study showed that the strength of material increases with the level of CW. The Bauschinger effect occurred when the strain path is reversed and its magnitude is independent on whether the tensile or compressive prestraining comes first or last but rather dependent on the amount of CW. The correlation between the CW levels and the lattice strain evolution during the in-situ loading showed that, the lattice strain increases with prestrain and reaches saturation in the material prestrained to 20%CW.The result of the mechanical failure test showed that, 20% cold rolled material loaded along the L and Transverse (T) directions showed a gradual failure, whilst the material loaded along the S direction exhibited a rapid failure. The SEM micrographs suggest that materials loaded along the L and T direction failed with the characteristic features of pure ductile failure while the specimen loaded along S direction showed mixed features of the ductile and brittle failure. The electrochemical properties of the cold rolled materials are more affected by sample orientation than the levels of CW. The short-transverse plane was observed to be most noble whilst the longitudinal plane was the least noble. The results of the SSRT in the chloride environment showed that the plastic elongation, the ultimate tensile strength and the time to failure decrease as the applied potential increases. The post-mortem analysis of the failed samples with the SEM showed that, the fracture surface contained region of ductile failure characterised by dimples, and region of SCC with secondary cracks along the loading axis. Whilst the cross sectional analysis, showed evidence of predominant transgranular stress corrosion cracks. The study found that SCC susceptibility of the ASS is directly linked to strain heterogeneity and directional anisotropy caused by cold working.
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Hartley, Deborah Jean. "Anxiety and depression: An empirical investigation of the Diathesis-Stress Model of psychopathology". CSUSB ScholarWorks, 1999. https://scholarworks.lib.csusb.edu/etd-project/1849.
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Taniguchi, Masayuki. "Dopamine D1 receptor subtype mediates acute stress-induced dendritic growth in excitatory neurons of the medial prefrontal cortex and contributes to suppression of stress susceptibility in mice". Kyoto University, 2018. http://hdl.handle.net/2433/232116.
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Gonzalez, Gabriel. "Alterations in Fatty Acid Amide Hydrolase (Faah) Transcript Levels and Activity Lead to Changes in the Abiotic Stress Susceptibility of Arabidopsis Thaliana". Thesis, University of North Texas, 2012. https://digital.library.unt.edu/ark:/67531/metadc115085/.
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N-Acylethanolamines (NAEs) are a class of bioactive lipids, and FAAH is one of the enzymes responsible for degrading NAEs in both plants and animals. in plants, FAAH appears to be closely associated with ABA, a phytohormone which has long been associated with plant stress responses, since the overexpression of FAAH in Arabidopsis results in ABA hypersensitivity. Therefore, it is reasonable to speculate that alterations in FAAH transcript levels will result in altered stress responses in plants. to investigate this hypothesis experiments were carried out in which wild type (WT), FAAH-overexpressing (OE), and T-DNA insertional FAAH knockouts of Arabidopsis (faah) were grown in MS media under stress conditions. the stress conditions tested included chilling stress, heavy metal stress induced by cadmium or copper, nutrient limitations induced by low phosphorus or low nitrogen, salt stress induced with NaCl, and osmotic stress induced with mannitol. the OE plants were consistently hypersensitive to all stress conditions in relation to wild type plants. Inactive FAAH overexpressors did not have the hypersensitivity to the salt and osmotic stress of the active OE plants and were instead tolerant to these stresses. FAAH2 (faah2) knockouts and FAAH 1 and 2 double knockouts (faah 1+2) were based on some root development parameters somewhat more tolerant than WT plants, but more sensitive in terms of shoot growth. Collectively the data suggests that FAAH activity may interact with stress-responsive pathways in plants, perhaps including pathways involving ABA.
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Cevik, Gul. "Investigation Of The Effect Of Orientation And Heat Treatment On The Stress Corrosion Cracking Susceptibility Of 7050 Aluminum Alloy". Master's thesis, METU, 2004. http://etd.lib.metu.edu.tr/upload/3/12605220/index.pdf.
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In the present work, the effect of variation in specimen orientation and heat treatment on the Stress Corrosion Cracking (SCC) susceptibility of 7050 aluminum alloy was investigated in 3,5% NaCl solution and under freely corroding conditions. For this purpose, Constant Extension Rate Tests (CERT) was performed on precracked Compact Tension (CT) specimens and the Direct Current Potential Drop technique was applied to measure the crack lengths. In addition to crack length versus time curves, the relationship between the crack growth rate and the stress intensity factor was determined. Fractographic analysis was utilized extensively to support the findings related with basic mechanisms of cracking.
The alloy was found to be in the most susceptible state in the SL orientation, in which the crack propagation direction is parallel to the rolling direction. The resistance to SCC is higher in the TS but at maximum in LT orientation where the loading direction is parallel to the rolling direction.
In the peak aging treatment, T651, alloy is susceptible to SCC in SL orientation. When the over aging treatment, T7651, is applied the resistance is increased and the two step over aging treatment, T73651, has resulted in an additional improvement in this orientation. On the other hand, the alloy showed higher resistance to SCC in TS and LT orientations in T651 condition compared to the T7651 and T73651 treatments. In these orientations, the alloy is less susceptible in T73651 condition than in T7651 treatment.
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Duff, Jonathon Andrew. "The influence of grain boundary structure in proton irradiated stainless steel on susceptibility to irradiation assisted stress corrosion cracking". Thesis, University of Manchester, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.496690.
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Della, Roverys Coseglio Mario Sergio. "Susceptibility of low-temperature plasma nitrided 17-4 PH (H1150D) to sulphide stress cracking (SSC) in typical oilfield environment". Thesis, University of Birmingham, 2018. http://etheses.bham.ac.uk//id/eprint/8488/.
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To attend the growing global demand for energy, oil production—expected to grow in the foreseeable future-relies on the extraction from unconventional resources, such as deep deposits off the coast and ultra-deep water. These environments are contaminated with significant amounts of hydrogen sulphide, a by–product that promotes hydrogen absorp- tion and subsequent failure by sulphide stress cracking (SSC). The 17-4 PH—a stainless steel widely used for oilfield components—is susceptible to SSC, in spite of its favourable combination of properties. In this study, plasma–based treatments, often used to improve wear resistance, were identified as potential methods to increase the resistance to SSC. To evaluate it, the 17-4 PH was surface–modified by conventional and low–temperature plasma nitriding (LTPN) and submitted to standard SSC experiments. LTPN resulted in superior resistance to SSC compared to both unmodified and HTPN conditions, at- tributed to the formation of a nitrogen–rich layer comprising mixed iron nitrides (ε–Fe2-3N and γ’–Fe4N) and expanded martensite without precipitation of chromium nitrides. The protection provided by this structure was mainly due to the compressive residual stress induced by nitriding, combined with the superior resistance to localise corrosion and the reduced hydrogen uptake by the substrate.
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Hilton, Bruce A. "Irradiation assisted stress corrosion cracking susceptibility of low fluence stainless steels evaluated by in-flux slow strain rate tests". Thesis, Massachusetts Institute of Technology, 1996. http://hdl.handle.net/1721.1/42810.
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Smith, Brian Donald. "The influence of high temperature stress and herbicides on the susceptibility of creeping bentgrass (Agrostis palustris) to Curvularia lunata". Thesis, Virginia Polytechnic Institute and State University, 1989. http://hdl.handle.net/10919/74538.
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The status of Curvularia lunata as a primary pathogen of creeping bentgrass (Agrostis palustris) has been debated in the literature for many years. The most recent and most complete evidence indicates that this fungus is a weak pathogen, colonizing only senescing tissues. In the present study, four groups of experiments were conducted: 1) The effects of five herbicides on the growth of C. lunata in vitro were determined. 2) Acute high temperature stress was evaluated as a predisposing factor in the susceptibility of creeping bentgrass to C. lunata. 3) The effects of acute high temperature stress and exposure to five different herbicides on creeping bentgrass were evaluated together and separately. 4) The potential of chronic, moderately high temperature stress and exposure to five herbicides when occurring separately and together to serve as predisposing factors on the susceptibility of creeping bentgrass to C. lunata were evaluated. It was found that effects of the herbicides on the growth of C. lunata depend on both the specific herbicide and the concentration. High temperature stress and herbicide exposure increase the colonization of creeping bentgrass by C. lunata only to the extent that these treatments produce moribund plant tissue.Master of Science
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Rojas-Rudolph, Isolde Gina. "Stress modulation of susceptibility to wound infection : effects on Leukocyte Trafficking and Chemokine Gene Expression during Cutaneous Wound Healing /". The Ohio State University, 2001. http://rave.ohiolink.edu/etdc/view?acc_num=osu1486474078047403.
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Tanaka, Kohei. "Prostaglandin E2-Mediated Attenuation of Mesocortical Dopaminergic Pathway is Critical for Susceptibility to Repeated Social Defeat Stress in Mice". Kyoto University, 2012. http://hdl.handle.net/2433/158067.
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PALADINI, MARIA SERENA. "STRESS EXPOSURE ACROSS LIFESPAN SHAPES THE CNS SUSCEPTIBILITY TO FURTHER ADVERSE EVENTS: PRECLINICAL EVIDENCE USING A DOUBLE HIT APPROACH". Doctoral thesis, Università degli Studi di Milano, 2019. http://hdl.handle.net/2434/694054.
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Stress exposure is known not only to be a risk factor for the development of psychiatric disorders itself, but also to exacerbate other medical conditions, prompting structural and functional changes that can eventually evolve from a normal adaptive body reaction to a pathological state (Gradus, 2017). On this basis, the aim of my PhD project was to investigate at preclinical level how and by which molecular mechanisms stress exposure can leave a signature in the individual, thus increasing the susceptibility of the central nervous system (CNS) to stress-related disorders or aggravating the outcome of illnesses occurring later in life. To achieve this goal, I took advantage of a “double hit” approach that implies that a ‘first hit’, mostly during critical periods of development, disrupts the ontogeny of neural systems and establishes a vulnerability to a ‘second hit’ later in life. Among the multiple mechanisms involved in stress- susceptibility, I have focused my analyses on neuroplasticity, neuroinflammation and oxidative damage. Moreover, considering that one of the most crucial variables of stress response extent is when the individual experiences it, I have investigated the long-lasting impact of stress occurring in different time windows. Specifically, I firstly focused on the gestational period, a so-called “window of vulnerability” (Briscoe et al., 2016) since the exposure to adverse events during pregnancy has been shown to impact not only on maternal health but also to have a deep long-lasting influence on the offspring neurodevelopment, leading to enhanced susceptibility to diseases and dysfunctions during adulthood (Zucchi et al., 2013; Coe and Lubach, 2005; Entringer et al., 2015). Therefore, in the first part of my project I examined the long-term effects of stress occurring during the intrauterine life on the clinical manifestations of a well-established animal model of multiple sclerosis, the Experimental Autoimmune Encephalomyelitis (EAE), a chronic and inflammatory condition characterized by loss of myelin (Robinson et al., 2014). My results 1 demonstrated that gestational stress induced a marked increase in the severity of EAE symptoms in the adult mouse. Further, I highlighted an altered maturation of oligodendrocytes in the spinal cord of prenatally stressed EAE animals. These behavioral and molecular alterations were paralleled by changes in the expression and signaling of the neurotrophin BDNF, an important mediator of neural plasticity that may contribute to stress-induced impaired remyelination (Murray and Holmes, 2011). Furthermore, since patients affected by stress-related disorders present deficit in the neuroplastic mechanisms that are normally set in motion in response to external challenging stimuli (Wang et al., 2017), I investigated the influence of stress in utero on the response to a second challenge in adulthood, exposing prenatally stressed mice to a further acute stress. The molecular analyses in the hippocampus revealed that fetal stress resulted not only in increased activation of the immune system itself, but also in an impairment of the proper responsiveness of the redox machinery to the second stress. I then focused on adolescence, a sensitive period for brain development and thus also for environmental stimuli including stress. Social stress, such as bullying or subordination, is among the most prevalent stressors throughout adolescence and is strongly related to an enhanced susceptibility to diseases and dysfunctions later in adulthood (Lupien et al., 2009). Moreover, adolescents are more prone to brain concussion, and indeed 15/19-year age juvenile are experiencing the highest rates of incidence of traumatic brain injury (TBI) (Kimbler et al., 2011). As such, I spent 6 months as a visiting PhD student at the laboratory of Brain Injury, Neuroinflammation and Cognitive Function headed by Professor Susanna Rosi at the University of California, San Francisco, to investigate if and how exposure to social stress during adolescence can alter the TBI outcome. Specifically, in this part of the PhD project, adolescent mice were exposed to the social defeat stress 2 protocol before being injured with a new model of TBI, the repetitive closed-head impact model of engineered rotational acceleration (CHIMERA). The results highlighted that stressed mice developed anxiety-like features, regardless the concussions, while stress and brain injury have a reciprocal influence in the NOR test, where only mice that were both stressed and exposed to TBI did not display impairment in the ability to recognize the novel object. Paralleled to these behavioral effects, we didn’t find differences in hippocampal microglia activation. Lastly, I have investigated stress exposure during adulthood, focusing on the potential long-lasting impact of a chronic stress paradigm -known to induce psychiatric-like phenotype in preclinical model- in altering the responsiveness to a second acute challenge after a recovery period of 3 weeks. The molecular analyses, focused on modulators of the oxidative balance, demonstrated that the second hit was able to strongly induce the gene expression of Sulfiredoxin 1 (Srxn1) and Metallothionein-1a (Mt-1a), two antioxidant genes. This beneficial effect set in motion to cope with the sudden challenging situation was impaired by the previous exposure to chronic stress. Interestingly, chronic treatment with the antipsychotic lurasidone partially restored the appropriate acute responsiveness. The results obtained during my PhD project by using the double hit approach in different periods of life, indicate neuroinflammation, altered oxidative balance and impaired neuroplasticity as common molecular targets underlying the impact of a previous stress in shaping the vulnerability to further adverse conditions, providing new information on the etiopathogenesis of stress-related diseases.
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Martínez, Membrives Esther. "Susceptibility to experimental autoimmune encephalomyelitis (model of multiple sclerosis) and anxiety in genetically heterogeneous rats". Doctoral thesis, Universitat Autònoma de Barcelona, 2012. http://hdl.handle.net/10803/123299.
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Las respuestas al estrés del eje hipotalámico-pituitario-adrenal (HPA) juegan un papel decisivo tanto en la conducta ansiosa como en el funcionamiento del sistema inmune (IS). Es sabido que los niveles elevados de glucocorticoides (GC) desempeñan un papel protector ante la encefalomielitis experimental autoinmune (EAE), fiable modelo animal de la esclerosis múltiple.
En esta Tesis, nos propusimos investigar si un determinado perfil ansioso podría corresponderse con un perfil específico de sensibilidad a la inflamación. En el “Estudio I”, ratas genéticamente heterogéneas N/Nih-HS de ambos sexos fueron inmunizadas con proteína oligodendrocito de la mielina (MOG) para evaluar la EAE. Con el objetivo de valorar los efectos de la ansiedad sobre el IS, examinamos la incidencia (INC) y la severidad de la EAE que presentaban los subgrupos de ratas con puntuaciones extremas en ansiedad. De estos subgrupos (de baja y alta ansiedad) también se comparó la conducta ansiosa y el peso relativo de las glándulas adrenales (RAW). Los resultados indicaron una posible relación entre alta ansiedad y resistencia a la EAE.
Sin embargo, algunas de las asociaciones asumidas en el “Estudio I” entre conducta ansiosa y estrés fisiológico, debían esclarecerse. Para ello, en el “Estudio II” se estudiaron las posibles relaciones entre las respuestas del eje HPA y la ansiedad las ratas inbred DA y PVG de ambos sexos. Las cepas DA y PVG son respectivamente susceptible y resistente a un amplio espectro de enfermedades autoinmunes, entre otras, la EAE. En el presente estudio, se caracterizaron estas cepas por sus conductas de miedo/ansiedad y actividad ante la novedad. Además se examinó la function del eje HPA, en terminos de niveles de corticosterona (basal y post-stress), peso relativo de las glándulas adrenales, y su expresión mRNA del receptor de la hormona adrenocorticotropa (MC2R). También se estudió la expresión mRNA de CD74 (complejo mayor de histocompatibilidad, clase II); y la interleucina proinflamatoria-6 (IL-6), en el núcleo paraventricular del hipotálamo, la pituitaria y las adrenales.
En conjunto, nuestros resultados muestran que en la EAE, un perfil ansioso se correspondería con un eje HPA incrementado, que podría actuar reprimiendo las respuestas inflamatorias, produciendo un efecto de cierta resistencia a la EAE.Stress hypothalamic-pituitary-adrenal (HPA) axis responses play a role in both anxiety behaviour and immune system (IS). Enhanced glucocorticoid (GC) levels have shown to play a protective role in experimental autoimmune encephalomyelitis (EAE), a reliable animal model of multiple sclerosis. In this Thesis, we aimed to investigate if a determined anxious profile could correspond to a specific inflammatory susceptibility. In “Study I”, genetically heterogeneous N/Nih-HS rats of both sexes were immunized with myelin oligodendrocyte glycoprotein (MOG) to evaluate EAE. To assess the effect of anxiety on IS, subgroups of rats scoring extreme values of anxiety were examined on their EAE incidence (INC) and severity. Also, anxious behaviour and relative adrenal weight (RAW) of subgroups selected by resistance or susceptibility was studied was compared. Results indicated a possible relationship between high anxiety and EAE-resistance. However, the assumed associations between behavioural anxiety and physiological stress needed to be elucidated. Thus, in “Study II” we studied in male and female DA and PVG inbred rats the possible relationships among HPA axis responses and anxiety. DA and PVG strains are respectively susceptible and resistant to a wide range of experimental autoimmune diseases, EAE among others. In the current study, these strains were characterized by their anxiety/inhibition. We further examined their HPA axis function, by means of (basal and post-stress) corticosterone levels, RAW, and via RT–PCR their expression of mRNA adrenocorticotropin receptor (Melanocortin 2 Receptor, MC2R) on adrenal glands. We also studied the mRNA expression of both CD74 (major histocompatibility complex; MHC-II) and the pro-inflammatory interleukin-6 (IL-6) on paraventricular nucleus of the hypothalamus (PVN), pituitary and adrenal glands. Together, our data show that in EAE, a high anxious profile accompanied by an enhanced HPA axis may involve the repression of inflammatory responses, providing a certain resistance.
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Hedborg, Kerstin. "Migraine and Stress : An Internet administered Multimodal Behavioral Treatment Intervention". Doctoral thesis, Uppsala universitet, Medicin, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-158079.
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Migraine is a disabling neurological disorder with high prevalence, the clinical manifestations of which are highly dependent on stress. The overall theme of the present thesis was to address aspects of stress in migraine. A multimodal behavioral treatment (MBT) program was developed specifically designed for migraine and focusing on stress as a trigger and an intervention was performed using this Internet-administered program. Migraine symptoms were followed via an Internet administered diary and questionnaires were answered at regular intervals during the 11-month study period. The thesis is based on four papers: In Paper I, life events and current stress, personality traits, and gender were studied cross-sectionally in 106 women and 44 men with migraine, who suffered at least two attacks a month at inclusion. Paper II describes a randomized controlled trial of the MBT program performed on 58 women and 25 men recruited from participants of the study described in Paper I. In the MBT study participants were randomized into one control group and two MBT groups, one of which received hand massage as part of the treatment. In Paper III, complete migraine drug use and changes in use and in drug efficacy during the MBT program were studied. In Paper IV, the salivary cortisol levels of MBT participants were evaluated as a biological stress marker. The MBT program proved effective in decreasing migraine headache; it was feasible and there was low attrition. Moreover, MBT resulted in decreased migraine drug use and increased drug efficacy, but had no discernible effects on salivary cortisol profiles. No effect of hand massage on migraine headache frequency was seen. Personality trait profiling revealed high scores for the neuroticism factor. Stress susceptibility was the single most aberrant personality trait and correlated highly with the reported level of current stress and with experienced negative life events. Gender differences included higher scores for women on trait anxiety, negative life events, depressive mood, anxiety, tension type headache, use of triptans, and efficacy of analgesics, whereas men displayed higher use of analgesics. In conclusion, the efficacy and low attrition associated with the present MBT program appears promising and timely with regard to the development of better and more accessible migraine treatment. Stress susceptibility, gender, negative life events and psychosomatic comorbidity are important factors to consider in relation to the care of persons with migraine.