Induction of cardiac Angptl4 by dietary fatty acids is mediated by peroxisome proliferator-activated receptor beta/delta and protects against fatty acid-induced oxidative stress.

RATIONALE: Although dietary fatty acids are a major fuel for the heart, little is known about the direct effects of dietary fatty acids on gene regulation in the intact heart. OBJECTIVE: To study the effect of dietary fatty acids on cardiac gene expression and explore the functional consequences. METHODS AND RESULTS: Oral administration of synthetic triglycerides composed of one single fatty acid altered cardiac expression of numerous genes, many of which are involved in the oxidative stress response. The gene most significantly and consistently upregulated by dietary fatty acids encoded Angiopoietin-like protein (Angptl)4, a circulating inhibitor of lipoprotein lipase expressed by cardiomyocytes. Induction of Angptl4 by the fatty acid linolenic acid was specifically abolished in peroxisome proliferator-activated receptor (PPAR)beta/delta(-/-) and not PPARalpha(-/-) mice and was blunted on siRNA-mediated PPARbeta/delta knockdown in cultured cardiomyocytes. Consistent with these data, linolenic acid stimulated binding of PPARbeta/delta but not PPARalpha to the Angptl4 gene. Upregulation of Angptl4 resulted in decreased cardiac uptake of plasma triglyceride-derived fatty acids and decreased fatty acid-induced oxidative stress and lipid peroxidation. In contrast, Angptl4 deletion led to enhanced oxidative stress in the heart, both after an acute oral fat load and after prolonged high fat feeding. CONCLUSIONS: Stimulation of cardiac Angptl4 gene expression by dietary fatty acids and via PPARbeta/delta is part of a feedback mechanism aimed at protecting the heart against lipid overload and consequently fatty acid-induced oxidative stress.

Eumelanin- and pheomelanin-based colour advertise resistance to oxidative stress in opposite ways.

The control mechanisms and information content of melanin-based colourations are still debated among evolutionary biologists. Recent hypotheses contend that molecules involved in melanogenesis alter other physiological processes, thereby generating covariation between melanin-based colouration and other phenotypic attributes. Interestingly, several molecules such as agouti and glutathione that trigger the production of reddish-brown pheomelanin have an inhibitory effect on the production of black/grey eumelanin, whereas other hormones, such as melanocortins, have the opposite effect. We therefore propose the hypothesis that phenotypic traits positively correlated with the degree of eumelanin-based colouration may be negatively correlated with the degree of pheomelanin-based colouration, or vice versa. Given the role played by the melanocortin system and glutathione on melanogenesis and resistance to oxidative stress, we examined the prediction that resistance to oxidative stress is positively correlated with the degree of black colouration but negatively with the degree of reddish colouration. Using the barn owl (Tyto alba) as a model organism, we swapped eggs between randomly chosen nests to allocate genotypes randomly among environments and then we measured resistance to oxidative stress using the KRL assay in nestlings raised by foster parents. As predicted, the degree of black and reddish pigmentations was positively and negatively correlated, respectively, with resistance to oxidative stress. Our results reveal that eumelanin- and pheomelanin-based colourations can be redundant signals of resistance to oxidative stress.

Ventilation, Oxidative Stress, and Nitric Oxide in Hypobaric versus Normobaric Hypoxia.

PURPOSE: Slight differences in physiological responses and nitric oxide (NO) have been reported at rest between hypobaric hypoxia (HH) and normobaric hypoxia (NH) during short exposure.Our study reports NO and oxidative stress at rest and physiological responses during moderate exercise in HH versus NH. METHODS: Ten subjects were randomly exposed for 24 h to HH (3000 m; FIO2, 20.9%; BP, 530 ± 6 mm Hg) or to NH (FIO2, 14.7%; BP, 720 ± 1 mm Hg). Before and every 8 h during the hypoxic exposures, pulse oxygen saturation (SpO2), HR, and gas exchanges were measured during a 6-min submaximal cycling exercise. At rest, the partial pressure of exhaled NO, blood nitrate and nitrite (NOx), plasma levels of oxidative stress, and pH levels were additionally measured. RESULTS: During exercise, minute ventilation was lower in HH compared with NH (-13% after 8 h, P < 0.05). End-tidal CO2 pressure was lower (P < 0.01) than PRE both in HH and NH but decreased less in HH than that in NH (-25% vs -37%, P < 0.05).At rest, exhaled NO and NOx decreased in HH (-46% and -36% after 24 h, respectively, P < 0.05) whereas stable in NH. By contrast, oxidative stress was higher in HH than that in NH after 24 h (P < 0.05). The plasma pH level was stable in HH but increased in NH (P < 0.01). When compared with prenormoxic values, SpO2, HR, oxygen consumption, breathing frequency, and end-tidal O2 pressure showed similar changes in HH and NH. CONCLUSION: Lower ventilatory responses to a similar hypoxic stimulus during rest and exercise in HH versus NH were sustained for 24 h and associated with lower plasma pH level, exaggerated oxidative stress, and impaired NO bioavailability.

Physiological parameters to select upland rice genotypes for tolerance to water deficit

Abstract: The objective of this work was to evaluate the feasibility of using physiological parameters for water deficit tolerance, as an auxiliary method for selection of upland rice genotypes. Two experiments - with or without water deficit - were carried out in Porangatu, in the state of Goiás, Brazil; the water deficit experiment received about half of irrigation that was applied to the well-watered experiment. Four genotypes with different tolerance levels to water stress were evaluated. The UPLRI 7, B6144F-MR-6-0-0, and IR80312-6-B-3-2-B genotypes, under water stress conditions, during the day, showed lower stomatal diffusive resistance, higher leaf water potential, and lower leaf temperature than the control. These genotypes showed the highest grain yields under water stress conditions, which were 534, 601, and 636 kg ha-1, respectively, and did not differ significantly among them. They also showed lower drought susceptibility index than the other genotypes. 'BRS Soberana' (susceptible control) was totally unproductive under drought conditions. Leaf temperature is a easy-read parameter correlated to plant-water status, viable for selecting rice genotypes for water deficit tolerance.

Neuroendocrine regulation and central dopamine (DA) systems in physical and psychological stress

Physical and psychological stress cause different patterns of changes in the fluorescence intensity of nigral and tuberoinfundibular DA neurons which point to changes in neuronal activity. In order to investigate possible interactions between alpha-MSH (alpha-melanotropin) and DA systems in stress, systemic and intraventricular injections of antiserum against alpha-MSH were made. The functional state of DA neurons was assessed by histochemical microfluorimetry and hormone levels were measured by radioimmunossay. Antiserum against alpha-MSH was found to affect the functional state of DA neurons, but only thorugh the intravenous route. Under physical stress i.v. injection of antiserum against alpha-MSH was accompanied by elevated levels of activity of the DA neurons of the substantia nigra. An intraventricular injection of the same antiserum was ineffective. In psychological stress, an effect was again seen only after intravenous injection of antiserum against alpha-MSH. In this situation, the activity in DA cell groups of the substantia nigra, ventral tegmental area and tubero-infundibular system was increased after antiserum injection. Possible influences from manipulations were checked; certain effects which depended upon experimental situation were noted. Our data suggest a modulatory influence of circulating alpha-MSH on the functional state of central DA systems.

Study of the physiological role of RasGAP cleavage

Résume Les caspases sont un groupe de protéases à cystéine qui s?activent lors de l'apoptose. Leur activation induit le clivage de nombreuses cibles intracellulaires, conduisant à l'activation de voies pro-apoptotiques et finalement au démantèlement des cellules. Cependant, des caspases ont été décrites dans de nombreux autres processus indépendants de l'apoptose, notamment dans la physiologie des cellules hématopoïétiques, des cellules musculaires, des cellules de la peau et des neurones. Comment est-ce que les cellules réconcilient-elles ces deux fonctions distinctes? Une partie de la réponse réside dans la nature des substrats qu'elles clivent. Certains substrats, une fois clivées, deviennent anti-apoptotiques. RasGAP est une cible des caspases et contient deux sites spécifiques de clivage par les caspases. Lorsque le niveau d?activité des caspases est faible le clivage de RasGAP produit un fragment N-terminal qui active un signal antiapoptotique, relayé par la voie de Ras/PI3K/Akt. Lorsque le niveau d?activité des caspases est plus élevé le fragment RasGAP N-terminal est à nouveau clivé, perdant de ce fait ses propriétés anti-apoptotiques. Dans cette étude, nous avons mis en évidence que l'activation de la voie Ras/PI3K/Akt induite par le fragment RasGAP N-terminal dépend de RasGAP lui-même. Par ailleurs, dans le but d?étudier l?importance du clivage de RasGAP dans un contexte physiologique, nous avons développé un modèle animal exprimant une gêne mutée de RasGAP de sorte que la protéine est devenu insensible a l?action de caspases. Les données préliminaires obtenues montrent que le clivage de RasGAP n'est pas indispensable pour le développement et l?homéostasie chez la souris. Finalement, nous avons développé une souris transgénique surexprimant le fragment de RasGAP N-terminal dans les cellules ß du pancréas. Les animaux obtenus ne montrent pas de symptômes dans les conditions basales bien qu?ils soient plus résistants au diabète induit expérimentalement. Ces résultats montrent que la surexpression du fragment N-terminal de RasGAP protége efficacement les cellules ß du pancréas de l?apoptose induite par le stress sans pourtant affecter d?autres paramètres physiologiques des Ilot de Langerhans.<br/><br/>Caspases are a series of proteases that are activated during apoptosis. Their activation causes the cleavage of numerous intracellular targets, which leads to cell dismantling and activation of pro-apoptotic pathways. Caspases have been found to be involved in the physiology of numerous cell types including haematopoietic cells, muscle cells, skin cells and neurons. How cells conciliate these two opposite functions? Part of the answer lies in the nature of the substrates they cleave. Some substrates become anti-apoptotic once cleaved by caspases. RasGAP is a caspase substrate that possesses two conserved caspase-cleavage sites. At low caspase activity, RasGAP is first cleaved and the generated N-terminal fragment activates a potent anti-apoptotic signal, mediated by the Ras/PI3K/Akt pathway. At higher caspase activity, the N-terminal fragment is further cleaved thereby losing its anti-apoptotic properties. In the present study we show that the activation of the Ras/PI3K/Akt pathway mediated by RasGAP N-terminal fragment is dependent on RasGAP itself. Moreover, to study the role of RasGAP cleavage in a physiological model, we have developed a knock-in mouse model expressing a RasGAP mutant that is not cleavable by caspases. Preliminary data shows that RasGAP cleavage is not required for normal development and homeostasis in mice. Finally, we have developed a transgenic mouse model overexpressing RasGAP N-terminal fragment in the ß-cell of the pancreas. In basal conditions, these mice show no difference with their wt counterparts. However, they are protected against experimentally induced diabetes. These results indicate that fragment N can protect ? cells from stress-induced apoptosis without affecting other physiological parameters of the Islets.

Use of physiological constraints to identify quantitative design principles for gene expression in yeast adaptation to heat shock

Background: Understanding the relationship between gene expression changes, enzyme activity shifts, and the corresponding physiological adaptive response of organisms to environmental cues is crucial in explaining how cells cope with stress. For example, adaptation of yeast to heat shock involves a characteristic profile of changes to the expression levels of genes coding for enzymes of the glycolytic pathway and some of its branches. The experimental determination of changes in gene expression profiles provides a descriptive picture of the adaptive response to stress. However, it does not explain why a particular profile is selected for any given response. Results: We used mathematical models and analysis of in silico gene expression profiles (GEPs) to understand how changes in gene expression correlate to an efficient response of yeast cells to heat shock. An exhaustive set of GEPs, matched with the corresponding set of enzyme activities, was simulated and analyzed. The effectiveness of each profile in the response to heat shock was evaluated according to relevant physiological and functional criteria. The small subset of GEPs that lead to effective physiological responses after heat shock was identified as the result of the tuning of several evolutionary criteria. The experimentally observed transcriptional changes in response to heat shock belong to this set and can be explained by quantitative design principles at the physiological level that ultimately constrain changes in gene expression. Conclusion: Our theoretical approach suggests a method for understanding the combined effect of changes in the expression of multiple genes on the activity of metabolic pathways, and consequently on the adaptation of cellular metabolism to heat shock. This method identifies quantitative design principles that facilitate understating the response of the cell to stress.

Traumatismes précoces et réponses de stress, leur association aves la santé mentale, l'attachement et l'ocytocine

Lorsqu'un individu est confronté à une situation stressante, une des réponses les plus saillantes est l'activation de l'axe HPA, caractérisée par le déclenchement d'un taux élevé de glucocorticoïdes dans le sang. De manière générale, cette réponse hormonale est adaptative et elle a pour but la mobilisation des ressources physiques et cognitives de l'individu pour une action spécifique (Axelrod & Reisine, 1984; Chrousos & Gold, 1992; N. M. Kaplan, 1988; McEwen, 2004). Cependant, lorsque une personne est confrontée très tôt dans son développement, et de manière répétée, à des situations de stress, cette réponse physiologique peut s'altérer, devenir inadaptée (Anand, 1993; Bremner et al., 1995; Meaney et al., 1996; Mirescu, Peters, & Gould, 2004; Plotsky & Meaney, 1993; Sapolsky, 2000) et être associée à des troubles cognitifs (McEwen & Sapolsky, 1995) et émotionnels (McEwen, 2000). A l'âge adulte, le résultat de ces altérations psychoneuroendocriniennes se traduit au cours de l'activation de l'axe HPA et elles sont visibles lors de situations de stress moins intenses (Graham, Heim, Goodman, Miller, & Nemeroff, 1999; Mirescu et al., 2004; Stam, Bruijnzeel, & Wiegant, 2000; A. Taylor, Fisk, & Glover, 2000). La dysregulation de l'axe HPA semble représenter un facteur de vulnérabilité lié à des dysfonctionnements psychiques et physiologiques chez les adultes (Heim, Ehlert, & Hellhammer, 2000; Heim & Nemeroff, 1999; Heim, Newport, Mletzko, Miller, & Hemeroff, 2008). Cependant, des facteurs de protection peuvent influencer à leur tour ces vulnérabilités. La littérature, basée sur des études translationnelles (animaux, humains), converge vers le postulat selon lequel la dimension relationnelle apportée par l'environnement est fondamentale dans le développement des vulnérabilités physiologiques et psychiques du sujet. Dans ce sens, les relations d'attachement ont été particulièrement étudiées. A l'âge adulte, par exemple, la qualité des représentations d'attachement semble influencer directement l'expression de gènes impliqués dans les réponses hormonales de stress (Biagini, Pich, Carani, Marrama, & Agnati, 1998; Caldji, Diorio, & Meaney, 2000; Dallman, 2000; De Kloet, Rosenfeld, Van Eekelen, Sutanto, & Levine, 1988; Rincon-Cortes & Sullivan, 2014; Romeo, Tang, & Sullivan, 2009; van Oers, de Kloet, Whelan, & Levine, 1998), illustrant ainsi une perspective épigénétique. Traumatismes précoces et réponses de stress, leur association avec la santé mentale, l'attachement et l'ocytocine Deux objectifs principaux définissent ce travail de doctorat. Le premier est de comprendre comment un événement à portée traumatique, qui a eu lieu pendant la période périnatale, l'enfance ou l'adolescence, peut s'inscrire au niveau physiologique (axe hypotalamico- hypophysaire-surrénalien - axe HPA), au niveau psychopathologique ou encore au niveau de la régulation émotionnelle au cours de l'âge adulte. A ce propos, nous avons évalué les réponses physiologiques (telles que le Cortisol, l'ACTH et l'ocytocine), la présence de psychopathologies (relatives à l'axe I du DSM-IV) et les réponses émotionnelles (telles que la perception au stress) au cours d'une situation de stress de nature psychosociale, induite en laboratoire. Le deuxième objectif de ce travail est de savoir si les représentations d'attachement peuvent médiatiser ces effets, chez des individus exposés à différents événements à portée traumatique. Dans ce but, trois populations ont été considérées. La première est relative à des jeunes adultes nés grands prématurés ; la deuxième, concerne des femmes adultes ayant vécu un ou plusieurs abus sexuels au cours de leur enfance ou de leur adolescence et enfin la troisième est constituée de personnes adultes qui ont survécu à une maladie grave (cancer) pendant leur enfance ou leur adolescence. Enfin, ces trois populations sont comparées à des groupes contrôle. La prise en considération de différents types de traumatismes a permis de relever : premièrement, qu'un événement à portée traumatique de nature différente, peut influencer de manière semblable les structures neuronales, par exemple l'hypocortisolémie ; deuxièmement, qu'un dysfonctionnement de l'axe HPA n'aboutit pas nécessairement à la présence de signes de souffrance mentale ; enfin, des effets protecteurs ont été mis en évidence. Ces facteurs sont sous-tendus, d'un point de vue psychologique, par les représentations d'attachement et, d'un point de vue physiologique, par la sécrétion d'ocytocjne périphérique. Traumatismes précoces et réponses de stress, leur association avec la santé mentale, l'attachement et l'ocytocine -- When an individual is faced by a stressful situation, one of the most notable responses is the activation of the HPA axis, which is characterized by a heightened level of glucocortisoids in the blood. In general, this is an adaptive hormonal response which prepares the individual both physically and cognitively for a specific action (Axelrod & Reisine, 1984; Chrousos & Gold, 1992; N. M. Kaplan, 1988; McEwen, 2004). However, should a person be confronted to stressful situations very early and repeatedly in their development, this physiologic response may be altered and become maladapted (Anand, 1993; Bremner et al., 1995; Meaney et al., 1996; Mirescu et al., 2004; Plotsky & Meaney, 1993; Sapolsky, 2000) which can be associated to emotional (McEwen, 2000) and cognitive disorders(McEwen & Sapolsky, 1995). Throughout adulthood, the result of these psychoneuroendocrine alterations affects the activation of the HPA axis and are noticeable during less intense stressful situations (Graham et al., 1999; Mirescu et al., 2004; Stam et al., 2000; A. Taylor et al., 2000). HPA axis dysregulation appears to represent a factor of vulnerability linked to psychological and physical disorders in adults (Heim, Ehlert, et al., 2000; Heim & Nemeroff, 1999; Heim, Newport, et al., 2008). Nonetheless, these vulnerabilities may be influenced by further protection factors. The literature, based on translational studies (animals and humans), suggests that relationships formed in the context of the individual's environment are fundamental in the development of their physiological and psychological vulnerabilities. Thus, attachment relationships have been particularly studied. In adulthood, for example, the quality of attachment representations appear to influence directly the expression of genes involved in the hormonal responses to stress (Biagini et al., 1998; Caldji et al., 2000; Dallman, 2000; De Kloet et al., 1988; Rincon-Cortes & Sullivan, 2014; Romeo et al., 2009; van Oers et al., 1998). With the goal to study these dimensions, two principal objectives define these doctoral study. The first is to understand how an event considered to be traumatic, which took place during early infancy, infancy, or adolescence, could influence physiology (HPA axis), psychopathology or emotional regulation during adulthood. Therefore we have evaluated the presence of psychopathologies (relative to axis I of the DSM), physiological responses (such as Cortisol, ACTH and oxytocin) and emotional responses (such as perception of stress) throughout a psychosocial stress situation, conducted in a laboratory setting. The second objective of this study is to understand if attachment representations can mediate these effects, in individuals exposed to three different types of traumatic events. Therefore, three populations have been considered. The first is young adults who were born prematurely; the second concerns adult women who have suffered sexual abuse, on one or more occasions, during their childhood or adolescence; finally the third group is constituted of people who have survived a grave childhood illness. These populations were all compared to control groups. The consideration of different types of traumatic events has demonstrated, firstly, that different events which are considered to be traumatic can similarly influence neuronal structures, for example hypocortisolism. Secondly, that an HPA axis disorder does not necessarily lead to the presence of mental signs of distress, as is the case for those born very prematurely. Finally, protective effects were demonstrated, distinctively from a psychological point of view, by attachment representations and furthermore by peripheral oxytocin secretion from a physiological perspective.

Relation between plaque type, plaque thickness, blood shear stress, and plaque stress in coronary arteries assessed by X-ray Angiography and Intravascular Ultrasound

Purpose: Atheromatic plaque progression is affected, among others phenomena, by biomechanical, biochemical, and physiological factors. In this paper, the authors introduce a novel framework able to provide both morphological (vessel radius, plaque thickness, and type) and biomechanical (wall shear stress and Von Mises stress) indices of coronary arteries. Methods: First, the approach reconstructs the three-dimensional morphology of the vessel from intravascular ultrasound(IVUS) and Angiographic sequences, requiring minimal user interaction. Then, a computational pipeline allows to automatically assess fluid-dynamic and mechanical indices. Ten coronary arteries are analyzed illustrating the capabilities of the tool and confirming previous technical and clinical observations. Results: The relations between the arterial indices obtained by IVUS measurement and simulations have been quantitatively analyzed along the whole surface of the artery, extending the analysis of the coronary arteries shown in previous state of the art studies. Additionally, for the first time in the literature, the framework allows the computation of the membrane stresses using a simplified mechanical model of the arterial wall. Conclusions: Circumferentially (within a given frame), statistical analysis shows an inverse relation between the wall shear stress and the plaque thickness. At the global level (comparing a frame within the entire vessel), it is observed that heavy plaque accumulations are in general calcified and are located in the areas of the vessel having high wall shear stress. Finally, in their experiments the inverse proportionality between fluid and structural stresses is observed.

Disturbance of wildlife by outdoor winter recreation: allostatic stress response and altered activity-energy budgets

Anthropogenic disturbance of wildlife is of growing conservation concern, but we lack comprehensive approaches of its multiple negative effects. We investigated several effects of disturbance by winter outdoor sports on free-ranging alpine Black Grouse by simultaneously measuring their physiological and behavioral responses. We experimentally flushed radio-tagged Black Grouse from their snow burrows, once a day, during several successive days, and quantified their stress hormone levels (corticosterone metabolites in feces [FCM] collected from individual snow burrows). We also measured feeding time allocation (activity budgets reconstructed from radio-emitted signals) in response to anthropogenic disturbance. Finally, we estimated the related extra energy expenditure that may be incurred: based on activity budgets, energy expenditure was modeled from measures of metabolism obtained from captive birds subjected to different ambient temperatures. The pattern of FCM excretion indicated the existence of a funneling effect as predicted by the allostatic theory of stress: initial stress hormone concentrations showed a wide inter-individual variation, which decreased during experimental flushing. Individuals with low initial pre-flushing FCM values augmented their concentration, while individuals with high initial FCM values lowered it. Experimental disturbance resulted in an extension of feeding duration during the following evening foraging bout, confirming the prediction that Black Grouse must compensate for the extra energy expenditure elicited by human disturbance. Birds with low initial baseline FCM concentrations were those that spent more time foraging. These FCM excretion and foraging patterns suggest that birds with high initial FCM concentrations might have been experiencing a situation of allostatic overload. The energetic model provides quantitative estimates of extra energy expenditure. A longer exposure to ambient temperatures outside the shelter of snow burrows, following disturbance, could increase the daily energy expenditure by >10%, depending principally on ambient temperature and duration of exposure. This study confirms the predictions of allostatic theory and, to the best of our knowledge, constitutes the first demonstration of a funneling effect. It further establishes that winter recreation activities incur costly allostatic behavioral and energetic adjustments, which call for the creation of winter refuge areas together with the implementation of visitor-steering measures for sensitive wildlife.

Oxidative Stress and Antioxidant Activity in Hypothermia and Rewarming. Can RONS Modulate the Beneficial Effects of Therapeutic Hypothermia?

Hypothermia is a condition in which core temperature drops below the level necessary to maintain bodily functions. The decrease in temperature may disrupt some physiological systems of the body, including alterations in microcirculation and reduction of oxygen supply to tissues. The lack of oxygen can induce the generation of reactive oxygen and nitrogen free radicals (RONS), followed by oxidative stress, and finally, apoptosis and/or necrosis. Furthermore, since the hypothermia is inevitably followed by a rewarming process, we should also consider its effects. Despite hypothermia and rewarming inducing injury, many benefits of hypothermia have been demonstrated when used to preserve brain, cardiac, hepatic, and intestinal function against ischemic injury. This review gives an overview of the effects of hypothermia and rewarming on the oxidant/antioxidant balance and provides hypothesis for the role of reactive oxygen species in therapeutic hypothermia.

Agricultural land use and human presence around breeding sites increase stress-hormone levels and decrease body mass in barn owl nestlings.

Human activities can have a suite of positive and negative effects on animals and thus can affect various life history parameters. Human presence and agricultural practice can be perceived as stressors to which animals react with the secretion of glucocorticoids. The acute short-term secretion of glucocorticoids is considered beneficial and helps an animal to redirect energy and behaviour to cope with a critical situation. However, a long-term increase of glucocorticoids can impair e.g. growth and immune functions. We investigated how nestling barn owls (Tyto alba) are affected by the surrounding landscape and by human activities around their nest sites. We studied these effects on two response levels: (a) the physiological level of the hypothalamus-pituitary-adrenal axis, represented by baseline concentrations of corticosterone and the concentration attained by a standardized stressor; (b) fitness parameters: growth of the nestlings and breeding performance. Nestlings growing up in intensively cultivated areas showed increased baseline corticosterone levels late in the season and had an increased corticosterone release after a stressful event, while their body mass was decreased. Nestlings experiencing frequent anthropogenic disturbance had elevated baseline corticosterone levels, an increased corticosterone stress response and a lower body mass. Finally, breeding performance was better in structurally more diverse landscapes. In conclusion, anthropogenic disturbance affects offspring quality rather than quantity, whereas agricultural practices affect both life history traits.

The caspase-3-p120-RasGAP module generates a NF-κB repressor in response to cellular stress.

The nuclear factor κB (NF-κB) transcription factor is a master regulator of inflammation. Short-term NF-κB activation is generally beneficial. However, sustained NF-κB might be detrimental, directly causing apoptosis of cells or leading to a persistent damaging inflammatory response. NF-κB activity in stressed cells needs therefore to be controlled for homeostasis maintenance. In mildly stressed cells, caspase-3 cleaves p120 RasGAP, also known as RASA1, into an N-terminal fragment, which we call fragment N. We show here that this fragment is a potent NF-κB inhibitor. Fragment N decreases the transcriptional activity of NF-κB by promoting its export from the nucleus. Cells unable to generate fragment N displayed increased NF-κB activation upon stress. Knock-in mice expressing an uncleavable p120 RasGAP mutant showed exaggerated NF-κB activation when their epidermis was treated with anthralin, a drug used for the treatment of psoriasis. Our study provides biochemical and genetic evidence of the importance of the caspase-3-p120-RasGAP stress-sensing module in the control of stress-induced NF-κB activation.

Keeping the balance? Management of oxidative stress, body mass and reproduction under energetic constraints by dispersing and philopatric collared flycatchers.

Dispersal, i.e. individual movement between breeding sites, is a key process for metapopulation dynamics and gene flow. Its success can be modulated by phenotypic differences between dispersing and philopatric individuals, or dispersal syndromes. However, the environmental (external) and physiological (internal) constraints underlying such syndromes remain poorly known. This project aimed at clarifying the impact of environmental variation and oxidative constraints, linked to the reactive oxygen species produced during respiration, on phenotypes associated to dispersal in a passerine bird, the collared flycatcher Ficedula albicollis. Energetic demand was experimentally (i) increased through a wing load manipulation or (ii) relieved through food supplementation. The oxidative balance of breeding flycatchers was influenced by complex interactions of dispersal status and extrinsic factors (breeding density, year, experimental treatments). Interestingly, antioxidant capacity was influenced both by permanent individual differences and by food availability, whereas measures of pro-oxidants were highly variables within individuals. Environmental variation and energetic constraints also modulated the differences in reproduction associated with dispersal: dispersing and philopatric birds differ in their management of the oxidative balance when it is competing with reproductive investment. This thesis highlights that reaction norms, rather than fixed differences, often shape traits associated to dispersal. ----- Le déplacement d'un individu entre sites de reproduction, ou dispersion, est un processus clé pour la dynamique des métapopulations et les flux de gènes. Son succès peut être modulé par des différences de phénotype, ou syndromes de dispersion. Cependant, les contraintes environnementales et physiologiques qui sous-tendent ces syndromes restent mal connues. Ce projet vise à clarifier l'impact des variations environnementales et des contraintes oxydatives (liées aux espèces réactives de l'oxygène produites durant la respiration) sur les phénotypes associés à la dispersion chez un passereau, le gobemouche à collier Ficedula albicollis. La demande énergétique a été expérimentalement (i) augmentée en manipulant la surface alaire ou (ii) diminuée par une supplémentation en nourriture. L'équilibre oxydo-réducteur des gobemouches en reproduction est influencé par des interactions complexes entre statut de dispersion et facteurs extrinsèques (densité de couples reproducteurs, année, traitement expérimental). La capacité antioxydante dépend principalement de différences permanentes entre individus, alors que les pro-oxydants présentent de grandes variations intra-individu. Environnement et contraintes énergétiques modulent aussi les différences de reproduction liées à la dispersion : les oiseaux dispersants et philopatriques diffèrent dans leur gestion de l'équilibre oxydo-réducteur lorsqu'il est en compétition avec l'investissement reproducteur. Ce travail souligne que les traits associés à la dispersion sont souvent déterminés par des normes de réaction à l'environnement et non des différences fixées entre individus.

Ecological and physiological variance in T-cell mediated immune response in Cory's shearwaters

T-cell mediated immune response (CMI) hasbeen widely studied in relation to individual andfitness components in birds. However, few studieshave simultaneously examined individual and socialfactors and habitat-mediated variance in theimmunity of chicks and adults from the samepopulation and in the same breeding season. Weinvestigated ecological and physiological variancein CMI of male and female nestlings and adults in abreeding population of Cory's Shearwaters(Calonectrisdiomedea) in theMediterranean Sea. Explanatory variables includedindividual traits (body condition, carbon andnitrogen stable isotope ratios, plasma totalproteins, triglycerides, uric acid, osmolarity,β-hydroxy-butyrate, erythrocyte meancorpuscular diameter, hematocrit, andhemoglobin) and burrow traits(temperature, isolation, and physicalstructure). During incubation, immune responseof adult males was significantly greater than thatof females. Nestlings exhibited a lower immuneresponse than adults. Ecological and physiologicalfactors affecting immune response differed betweenadults and nestlings. General linear models showedthat immune response in adult males was positivelyassociated with burrow isolation, suggesting thatmales breeding at higher densities suffer immunesystem suppression. In contrast, immune response inchicks was positively associated with bodycondition and plasma triglyceride levels.Therefore, adult immune response appears to beassociated with social stress, whereas a trade-offbetween immune function and fasting capability mayexist for nestlings. Our results, and those fromprevious studies, provide support for anasymmetrical influence of ecological andphysiological factors on the health of differentage and sex groups within a population, and for theimportance of simultaneously considering individualand population characteristics in intraspecificstudies of immune response.