Life without Phd? – Phd Oxygen Sensor Proteins in Hypoxic Carcinoma Cell Survival

The microenvironment within the tumor plays a central role in cellular signaling. Rapidly proliferating cancer cells need building blocks for structures as well as nutrients and oxygen for energy production. In normal tissue, the vasculature effectively transports oxygen, nutrient and waste products, and maintains physiological pH. Within a tumor however, the vasculature is rarely sufficient for the needs of tumor cells. This causes the tumor to suffer from lack of oxygen (hypoxia) and nutrients as well as acidification, as the glycolytic end product lactate is accumulated. Cancer cells harbor mutations enabling survival in the rough microenvironment. One of the best characterized mutations is the inactivation of the von Hippel-Lindau protein (pVHL) in clear cell renal cell carcinoma (ccRCC). Inactivation causes constitutive activation of hypoxia-inducible factor HIF which is an important survival factor regulating glycolysis, neovascularization and apoptosis. HIFs are normally regulated by HIF prolyl hydroxylases (PHDs), which in the presence of oxygen target HIF α-subunit to ubiquitination by pVHL and degradation by proteasomes. In my thesis work, I studied the role of PHDs in the survival of carcinoma cells in hypoxia. My work revealed an essential role of PHD1 and PHD3 in cell cycle regulation through two cyclin-dependent kinase inhibitors (CKIs) p21 and p27. Depletion of PHD1 or PHD3 caused a cell cycle arrest and subjected the carcinoma cells to stress and impaired the survival.

Mechanisms of endothelin-1 induced reactive oxygen species production in vascular adventitial fibroblasts

With the relationship between endothelin-1 (ET-1) stimulation and reactive oxygen species (ROS) production unknown in adventitial fibroblasts, I examined the ROS response to ET-1 and angiotensin (Ang II). ET-1 -induced ROS peaked following 4 hrs of ET-1 stimulation and was inhibited by an ETA receptor antagonist (BQ 123, 1 uM) an extracellular signal-regulated kinase (ERK) 1/2 inhibitor (PD98059, 10 uM), and by both a specific, apocynin (10 uM), and non-specific, diphenyleneiodonium (10 uM), NAD(P)H oxidase inhibitor. NOX2 knockout fibroblasts did not produce an ET-1 induced change in ROS levels. Ang II treatment increased ROS levels in a biphasic manner, with the second peak occurring 6 hrs following stimulation. The secondary phase of Ang II induced ROS was inhibited by an ATi receptor antagonist, Losartan (100 uM) and BQ 123. In conclusion, ET-1 induces ROS production primarily through an ETA-ERKl/2 NOX2 pathway, additionally, Ang II-induced ROS production also involves an ETa pathway.

Lifespan, body size and oxygen : aerobic metabolism and oxidative stress in cultured fibroblasts /

The allometric scaling relationship observed between metabolic rate (MR) and species body mass can be partially explained by differences in cellular MR (Porter & Brand, 1995). Here, I studied cultured cell lines derived from ten mammalian species to determine whether cells propagated in an identical environment exhibited MR scaling. Oxidative and anaerobic metabolic parameters did not scale significantly with donor body mass in cultured cells, indicating the absence of an intrinsic MR setpoint. The rate of oxygen delivery has been proposed to limit cellular metabolic rates in larger organisms (West et al., 2002). As such cells were cultured under a variety of physiologically relevant oxygen tensions to investigate the effect of oxygen on cellular metabolic rates. Exposure to higher medium oxygen tensions resulted in increased metabolic rates in all cells. Higher MRs have the potential to produce more reactive oxygen species (ROS) which could cause genomic instability and thus reduced lifespan. Longer-lived species are more resistant to oxidative stress (Kapahi et al, 1999), which may be due to greater antioxidant and/or DNA repair capacities. This hypothesis was addressed by culturing primary dermal fibroblasts from eight mammalian species ranging in maximum lifespan from 5 to 120 years. Only the antioxidant manganese superoxide dismutases (MnSOD) positively scaled with species lifespan (p<0.01). Oxidative damage to DNA is primarily repaired by the base excision repair (BER) pathway. BER enzyme activities showed either no correlation or as in the case of polymerase p correlated, negatively with donor species (p<0.01 ). Typically, mammalian cells are cultured in a 20% O2 (atmospheric) environment, which is several-fold higher than cells experience in vivo. Therefore, the secondary aim of this study was to determine the effect of culturing mammalian cells at a more physiological oxygen tension (3%) on BER, and antioxidant, enzyme activities. Consistently, standard culture conditions induce higher antioxidant and DNA ba.se excision repair activities than are present under a more physiological oxygen concentration. Therefore, standard culture conditions are inappropriate for studies of oxidative stress-induced activities and species differences in fibroblast DNA BER repair capacities may represent differences in ability to respond to oxidative stress. An interesting outcome firom this study was that some inherent cellular properties are maintained in culture (i.e. stress responses) while others are not (i.e. MR).

Biogeochemistry of Paleozoic brachiopods from New York State and Ontario

A comprehensive elemental, isotopic and microstructural analyses was undertaken of brachiopod calcites from the Hamilton Group (Middle Devonian), Clinton Group (Middle Silurian) and Middle to Upper Ordovician strata of Ontario and New York State. The majority of specimens were microstructurally and chemically preserved in a pristine state, although a number of specimens show some degree of post-depositional alteration. Brachiopod calcites from the Hamilton and Clinton Groups were altered by marine derived waters whereas Trenton Group (Middle Ordovician) brachiopods altered in meteorically derived fluids. Analysis of the elemental and isotopic compositions of pristine Hamilton Group brachiopods indicates there are several chemical relationships inherent to brachiopod calcite. Taxonomic differentiation of Mg, Sr and Na contents was evident in three co-occuring species from the Hamilton Group. Mean Mg contents of pristine brachiopods were respectively Athyris spiriferoides (1309ppm), Mucrospirifer mucronatus (1035ppm) and Mediospirifer audacula (789ppm). Similarly, taxonomic differentiation of shell calcite compositions was observed in co-occuring brachiopods from the Clinton Group (Middle Silurian) and the Trenton Group (Middle Ordovician). The taxonomic control of elemental regulation into shell calcite is probably related to the slightly different physiological systems and secretory mechanisms. A relationship was observed in Hamilton Group species between the depth of respective brachiopod communities and their Mg, Sr and Na contents. These elements were depleted in the shell calcites of deeper brachiopods compared to their counterparts in shallower reaches. Apparently shell calcite elemental composition is related to environmental conditions of the depositional setting, which may have controlled the secretory regime, mineral morphology of shell calcite and precipitation rates of each species. Despite the change in Mg, Sr and Na contents between beds and formations in response to environmental conditions, the taxonomic differentiation of shell calcite composition is maintained. Thus, it may be possible to predict relative depth changes in paleoenvironmental reconstructions using brachiopod calcite. This relationship of brachiopod chemistry to depth was also tested within a transgressiveregressive (T-R) cycle in the Rochester Shale Formation (Middle Silurian). Decreasing Mg, Sr and Na contents were observed in the transition from the shallow carbonates of the Irondequoit Formation to the deeper shales of the lowest 2 m of Rochester Shale. However, no isotopic and elemental trends were observed within the entire T-R cycle which suggests that either the water conditions did not change significantly or that the cycle is illusory. A similar relationship was observed between the Fe and Mn chemistries of shell calcite and redox/paleo-oxygen conditions. Hamilton Group brachiopods analysed from deeper areas of the shelf are enriched in Mn and Fe relative to those from shallow zones. The presence of black shales and dysaerobic faunas, during deposition of the Hamilton Group, suggests that the waters of the northern Appalachian Basin were stratified. The deeper brachiopods were marginally positioned above an oxycline and their shell calcites reflect periodic incursions of oxygen depleted water. Furthermore, analysis of Dalmanella from the black shales of the Collingwood Shale (Upper Ordovician) in comparison to those from the carbonates of the Verulam Formation (Middle Ordovician) confirm the relationship of Fe and Mn contents to periodic but not permanent incursions of low oxygen waters. The isotopic compositions of brachiopod calcite found in Hamilton Group (813C; +2.5% 0 to +5.5% 0; 8180 -2.50/00 to -4.00/00) and Clinton Group (813C; +4.00/00 to +6.0; 8180; -1.8% 0 to -3.60/ 00) are heavier than previously reported. Uncorrected paleotemperatures (assuming normal salinity, 0% 0 SMOW and no fractionation effects) derived from these isotopic values suggest that the Clinton sea temperature (Middle Silurian) ranged from 18°C to 28°C and Hamilton seas (Middle Devonian) ranged between 24°C and 29°C. In addition, the isotopic variation of brachiopod shell calcite is significant and is related to environmental conditions. Within a single time-correlative shell bed (the Demissa Bed; Hamilton Group) a positive isotopic shift of 2-2.5% 0 in 013C compositions and a positive shift of 1.0-1.50/00 in 0180 composition of shell calcite is observed, corresponding with a deepening of brachiopod habitats toward the axis of the Appalachian Basin. Moroever, a faunal succession from deeper Ambocoelia dominated brachiopod association to a shallow Tropidoleptus dominated assocation is reflected by isotopic shifts of 1.0-1.50/00. Although, other studies have emphasized the significance of ±20/oo shifts in brachiopod isotopic compositions, the recognition of isotopic variability in brachiopod calcite within single beds and within depositional settings such as the Appalachian Basin has important implications for the interpretation of secular isotopic trends. A significant proportion of the variation observed isotopic distribution during the Paleozoic is related to environmental conditions within the depositional setting.

Response rainbow trout (Salmon gairdneri) blood gas transport system to temperature, oxygen availability and photoperiod

Hematological status in rainbow trout, Salmo gairdneri, was examined in relation to eight combinations of three environmental fa ctors; temperature (5°, 20°C), oxygen availability «35%, >70% saturation) and photoperiod (16L:8D, 8L:16D) and evaluated by 3-factor analysis of variance. Hemog l obin and hematocrit , indicators of oxygenc arrying capacity increased significantly at the higher temperature, following exposure to hypoxia and in relation to reduced light period. Significant variations in mean corpuscular hemoglobin concentration were not detected. The effects of temperature and oxygen availability were more pronounced than that of photoperiod which was generally masked. Although oxygen availability and photoperiod did not interact with temperature, the interaction of the former fac tors was significant. Elec trophoresis revealed twelve hemoglobin isomorphs. Relative concentration changes were found in re lation to the factors c onsidered with temperature>hypoxia>photoperiod. Howeve r , in terms of absolute concentration, effects were hypoxia>temperature>photoperiod. Photoperiod effects were again masked by temperature and (or) hypoxia. Red cell +2 l eve ls of [CI ] and [Mg ], critical elements in the hemoglobin-oxygen affinity regulating system, were also significantly altered. Red cell CI +2 was influenced only by temperature ; Mg by temper ature and oxygen. No photoperiod influence on either ions was observed. Under nominal 'summer' conditions, these changes point to the likelihood of increases in oxygen-c arrying c apac ity coupled with low Hb-02 affinity adjustments which would be expected to increase oxygen delivery rates to their more rapidly metabolising tissues.

The satellite band patterns in the near ultraviolet absorption spectra of isotopic compounds of acetaldehyde

The 3700 A - 3000 A absorption spectra of CH3CHO and its isotopic compounds such as CH3CDO, CD3CHO and CD3CDO were studied in the gas phase at room temperature and low temperatures. The low resolution spectra of the compounds were recorded by a 1.5 m Baush and Lomb grating spectrograph. The high resolution spectra were recorded by a Ebert spectrograph with the Echelle grating and the holographic grating separately. The multiple reflection cells were used to achieve the long path length. The pressure-path length used for the absorption spectrum of CH 3CHO was up to 100 mm Hg )( 91 . 43mo The emission spectrum and the excitation spectrum of CH3CHO were also recorded in this research. The calculated satellite band patterns \vhich were ob-tailied by the method of Lewis were used to compare with the observed near UV absorption spectrum of acetaldehyde. These calculated satellite band patterns belonged to two cases: namely, the barriers-in-phase case and the barriers- out-of-phase case. Each of the calculated patterns corresponded to a stable conformation of acetaldehyde in the excited state . The comparisons showed that the patterns in the observed absorption spectra corresponded to the H-H eclipsed conformations of acetaldehyde in the excited state . The least squares fitting analysis showed that the barrier heights in the excited state were higher than in the ground state. Finally, the isotopic shifts for the isotopic compounds of acetaldehyde were compared to the compounds with the similar deuterium substitution.

Oxygen exchange in galls of Eurosta solidaginis (Diptera: Tephritidae)

Hypoxia in plant tissue should affect animals living within. Gallmakers stimulate their plant hosts to produce the gall they inhabit and feed on, and also influence the gall phenotype for other adaptations, such as defense against predators. The potential for hypoxia in galls of Eurosta solidaginis was studied in the context of potential adaptations to gall oxygen level, using a combination of direct measurement, mathematical modelling, and respirometry on both gallmakers and hosts. Modelling results suggested mild hypoxia tolerable to the larva persists for most of the growth season, whereas more severe hypoxia may occur earlier in fully-grown young galls. Field data from one of the two years studied showed hypoxia more severe than expected, and coincided with adverse weather conditions and high larval mortality. The hypoxia may be related to host response to adverse weather. Whether hypoxia directly caused larval mortality requires further study.

Cellular Mechanisms of Resveratrol's Interaction with Mitochondrial Reactive Oxygen Species Metabolism

Resveratrol, a polyphenol found naturally in red wines, has attracted great interest in both the scientific community and the general public for its reported ability to protect against many of the diseases facing Western society today. While the purported health effects of resveratrol are well characterized, details of the cellular mechanisms that give rise to these observations are unclear. Here, the mitochondrial antioxidant enzyme Mn superoxide dismutase (MnSOD) was identified as a proximal target of resveratrol in vitro and in vivo. MnSOD protein and activity levels increase significantly in cultured cells treated with resveratrol, and in the brain tissue of mice given resveratrol in a high fat diet. Preventing the increase in MnSOD levels eliminates two of resveratrol’s more interesting effects in the context of human health: inhibition of proliferative cell growth and cytoprotection. Thus, the induction of MnSOD is a critical step in the molecular mechanism of resveratrol. Mitochondrial morphology is a malleable property that is capable of impeding cell cycle progression and conferring resistance against stress induced cell death. Using confocal microscopy and a novel ‘cell free’ fusion assay it was determined that concurrent with changes in MnSOD protein levels, resveratrol treatment leads to a more fused mitochondrial reticulum. This observation may be important to resveratrol’s ability to slow proliferative cell growth and confer cytoprotection. Resveratrol's biological activities, including the ability to increase MnSOD levels, are strikingly similar to what is observed with estrogen treatment. Resveratrol fails to increase MnSOD levels, slow proliferative cell growth and confer cytoprotection in the presence of an estrogen receptor antagonist. Resveratrol's effects can be replicated with the specific estrogen receptor beta agonist diarylpropionitrile, and are absent in myoblasts lacking estrogen receptor beta. Four compounds that are structurally similar to resveratrol and seven phytoestrogens predicted to bind to estrogen receptor beta were screened for their effects on MnSOD, proliferative growth rates and stress resistance in cultured mammalian cells. Several of these compounds were able to mimic the effects of resveratrol on MnSOD levels, proliferative cell growth and stress resistance in vitro. Thus, I hypothesize that resveratrol interacts with estrogen receptor beta to induce the upregulation of MnSOD, which in turn affects cell cycle progression and stress resistance. These results have important implications for the understanding of RES’s biological activities and potential applications to human health.

Chasseurs de bisons : apports de l’archéozoologie et de la biogéochimie isotopique à l’étude palethnographique et paléoéthologique du gisement épigravettien d’Amvrosievka (Ukraine)

Réalisé en cotutelle avec le Département de Préhistoire du Muséum national d’Histoire naturelle (Paris, France), École doctorale « Sciences de la nature et de l’Homme » (ED 227)

Detection and quantification of staphylococcus aureus enterotoxin B in food product using isotopic dilution techniques and mass spectrometry

L’entérotoxine B staphylococcique (SEB) est une toxine entérique hautement résistante à la chaleur et est responsable de plus de 50 % des cas d’intoxication d’origine alimentaire par une entérotoxine. L’objectif principal de ce projet de maîtrise est de développer et valider une méthode basée sur des nouvelles stratégies analytiques permettant la détection et la quantification de SEB dans les matrices alimentaires. Une carte de peptides tryptiques a été produite et 3 peptides tryptiques spécifiques ont été sélectionnés pour servir de peptides témoins à partir des 9 fragments protéolytiques identifiés (couverture de 35 % de la séquence). L’anhydride acétique et la forme deutérée furent utilisés afin de synthétiser des peptides standards marqués avec un isotope léger et lourd. La combinaison de mélanges des deux isotopes à des concentrations molaires différentes fut utilisée afin d’établir la linéarité et les résultats ont démontré que les mesures faites par dilution isotopique combinée au CL-SM/SM respectaient les critères généralement reconnus d’épreuves biologiques avec des valeurs de pente près de 1, des valeurs de R2 supérieure à 0,98 et des coefficients de variation (CV%) inférieurs à 8 %. La précision et l’exactitude de la méthode ont été évaluées à l’aide d’échantillons d’homogénat de viande de poulet dans lesquels SEB a été introduite. SEB a été enrichie à 0,2, 1 et 2 pmol/g. Les résultats analytiques révèlent que la méthode procure une plage d’exactitude de 84,9 à 91,1 %. Dans l’ensemble, les résultats présentés dans ce mémoire démontrent que les méthodes protéomiques peuvent être utilisées efficacement pour détecter et quantifier SEB dans les matrices alimentaires. Mots clés : spectrométrie de masse; marquage isotopique; protéomique quantitative; entérotoxines

Immigration et alimentation à Montréal aux XVIIe et XVIIIe siècles : essai d’interprétation à partir d’analyses isotopiques sur des populations archéologiques

Afin d’étudier l’influence de la migration sur l’alimentation à Montréal aux XVIIe et XVIIIe siècles, 64 individus de la collection du cimetière Notre-Dame, daté de 1691 à 1796, ont fait l’objet d’analyses ostéologiques et isotopiques. Les analyses isotopiques ont portées sur le carbone (d13C) et l’azote (d15N) du collagène des os, ainsi que sur le d13C et l’oxygène (d18O) du carbonate de l’apatite des os et des dents (prémolaires et troisièmes molaires). Le d18O des dents a permis de définir approximativement trois régions d’origine (région de Montréal, région enrichie en 18O (i.e. Acadie, Louisiane, Nouvelle-Angleterre, France, Antilles et Afrique) et région appauvrie en 18O (intérieur des terres et plus au nord) pour 58 individus, et sept possibles parcours migratoire (N=27). Plus de la moitié de l’échantillon est composé d’individus possiblement natifs de Montréal (55 %). De plus, les résultats indiquent que les gens étaient peu mobiles avant l’âge de 16 ans. Toutefois, 12 individus ont entrepris des déplacements entre 7 et 16 ans, majoritairement d’un environnement enrichi vers Montréal (N=5) ou de Montréal vers une région appauvrie (N=5). L’âge de recrutement des mousses sur les navires, la traite de la fourrure, la coupe du bois et possiblement aussi l’esclavage pourraient expliquer cette « jeune » migration. Sur le plan alimentaire, les végétaux de type C3, la viande nourrie aux ressources C3 et le poisson faisaient partie du menu montréalais. Les plantes C4 (majoritairement maïs mais aussi sucre de canne [rhum]) étaient consommées en quantité variable. La question de l’influence de la migration sur l’alimentation n’a pu être explorée en profondeur en raison de contraintes liées à la contamination du d18O du carbonate des os. La combinaison des données ostéologiques et isotopiques à la distribution spatiale des sépultures, a permis d’étudier un aspect de l’archéologie funéraire à l’échelle individuelle (identité possible), sans toutefois fournir de résultats probants, à l’échelle du cimetière et de son organisation globale.

The effect of oxygen and parenteral nutrition on the redox potential and bronchopulmonary dysplasia in extremely preterm infants

Introduction: Le supplément d’oxygène et la nutrition parentérale (NP) sont les deux sources majeures de stress oxydant chez le nouveau-né. Lors de la détoxification des oxydants, le potentiel redox du glutathion s’oxyde. Notre hypothèse est que le supplément d’oxygène et la durée de la NP sont associés à un potentiel redox plus oxydé et à une augmentation de la sévérité de la dysplasie bronchopulmonaire (DBP). Patients et Méthodes: Une étude observationnelle prospective incluant des enfants de moins de 29 semaines d’âge gestationnel. Les concentrations sanguines de GSH et GSSG à jour 6-7 et à 36 semaines d’âge corrigé étaient mesurées par électrophorèse capillaire et le potentiel redox était calculé selon l’équation de Nernst. La sévérité de la DBP correspondait à la définition du NICHD. Résultats: Une FiO2≥ 25% au 7ième jour de vie ainsi que plus de 14 jours de NP sont significativement associés à un potentiel redox plus oxydé et à une DBP plus sévère. Ces relations sont indépendantes de l’âge de gestation et de la gravité de la maladie initiale. La corrélation entre le potentiel redox et la sévérité de la DBP n’est pas significative. La durée de la NP était responsable de 15% de la variation du potentiel redox ainsi que de 42% de la variation de la sévérité de la DPB. Conclusion: Ces résultats suggèrent que l’oxygène et la NP induisent un stress oxydant et que les stratégies visant une utilisation plus judicieuse de l’oxygène et de la NP devraient diminuer la sévérité de la DBP.

Evaluation of mitochondrial function in a model of developmental programming of hypertension associated with transient neonatal oxygen exposure

UNE EXPOSITION NÉONATALE À L’OXYGÈNE MÈNE À DES MODIFICATIONS DE LA FONCTION MITOCHONDRIALE CHEZ LE RAT ADULTE Introduction: L’exposition à l’oxygène (O2) des ratons nouveau-nés a des conséquences à l’âge adulte dont une hypertension artérielle (HTA), une dysfonction vasculaire, une néphropénie et des indices de stress oxydant. En considérant que les reins sont encore en développement actif lors des premiers jours après la naissance chez les rats, jouent un rôle clé dans le développement de l’hypertension et qu’une dysfonction mitochondriale est associé à une augmentation du stress oxydant, nous postulons que les conditions délétères néonatales peuvent avoir un impact significatif au niveau rénal sur la modulation de l’expression de protéines clés du fonctionnement mitochondrial et une production mitochondriale excessive d’espèces réactives de l’ O2. Méthodes: Des ratons Sprague-Dawley sont exposés à 80% d’O2 (H) ou 21% O2 (Ctrl) du 3e au 10e jr de vie. En considérant que plusieurs organes des rats sont encore en développement actif à la naissance, ces rongeurs sont un modèle reconnu pour étudier les complications d’une hyperoxie néonatale, comme celles liées à une naissance prématurée chez l’homme. À 4 et à 16 semaines, les reins sont prélevés et les mitochondries sont extraites suivant une méthode d’extraction standard, avec un tampon contenant du sucrose 0.32 M et différentes centrifugations. L’expression des protéines mitochondriales a été mesurée par Western blot, tandis que la production d’ H202 et les activités des enzymes clés du cycle de Krebs ont été évaluées par spectrophotométrie. Les résultats sont exprimés par la moyenne ± SD. Résultats: Les rats mâles H de 16 semaines (n=6) présentent une activité de citrate synthase (considéré standard interne de l’expression protéique et de l’abondance mitochondriales) augmentée (12.4 ± 8.4 vs 4.1 ± 0.5 μmole/mL/min), une diminution de l’activité d’aconitase (enzyme sensible au redox mitochondrial) (0.11 ± 0.05 vs 0.20 ± 0.04 μmoles/min/mg mitochondrie), ainsi qu’une augmentation dans la production de H202 (7.0 ± 1.3 vs 5.4 ± 0.8 ρmoles/mg protéines mitochondriales) comparativement au groupe Ctrl (n=6 mâles et 4 femelles). Le groupe H (vs Ctrl) présente également une diminution dans l’expression de peroxiredoxin-3 (Prx3) (H 0.61±0.06 vs. Ctrl 0.78±0.02 unité relative, -23%; p<0.05), une protéine impliquée dans l’élimination d’ H202, de l’expression du cytochrome C oxidase (Complexe IV) (H 1.02±0.04 vs. Ctrl 1.20±0.02 unité relative, -15%; p<0.05), une protéine de la chaine de respiration mitochondriale, tandis que l’expression de la protéine de découplage (uncoupling protein)-2 (UCP2), impliquée dans la dispersion du gradient proton, est significativement augmentée (H 1.05±0.02 vs. Ctrl 0.90±0.03 unité relative, +17%; p<0.05). Les femelles H (n=6) (vs Ctrl, n=6) de 16 semaines démontrent une augmentation significative de l’activité de l’aconitase (0.33±0.03 vs 0.17±0.02 μmoles/min/mg mitochondrie), de l’expression de l’ATP synthase sous unité β (H 0.73±0.02 vs. Ctrl 0.59±0.02 unité relative, +25%; p<0.05) et de l’expression de MnSOD (H 0.89±0.02 vs. Ctrl 0.74±0.03 unité relative, +20%; p<0.05) (superoxide dismutase mitochondriale, important antioxidant), tandis que l’expression de Prx3 est significativement réduite (H 1.1±0.07 vs. Ctrl 0.85±0.01 unité relative, -24%; p<0.05). À 4 semaines, les mâles H (vs Ctrl) présentent une augmentation significative de l’expression de Prx3 (H 0.72±0.03 vs. Ctrl 0.56±0.04 unité relative, +31%; p<0.05) et les femelles présentent une augmentation significative de l’expression d’UCP2 (H 1.22±0.05 vs. Ctrl 1.03±0.04 unité relative, +18%; p<0.05) et de l’expression de MnSOD (H 1.36±0.01 vs. 1.19±0.06 unité relative, +14%; p<0.05). Conclusions: Une exposition néonatale à l’O2 chez le rat adulte mène à des indices de dysfonction mitochondriale dans les reins adultes, associée à une augmentation dans la production d’espèces réactives de l’oxygène, suggérant que ces modifications mitochondriales pourraient jouer un rôle dans l’hypertension artérielle et d’un stress oxydant, et par conséquent, être un facteur possible dans la progression vers des maladies cardiovasculaires. Mots-clés: Mitochondries, Reins, Hypertension, Oxygène, Stress Oxydant, Programmation

Essai de détection de processus migratoires à travers les isotopes de strontium et d’oxygène : étude des restes humains du cimetière Saint-Matthew (Québec, 1771-1860)

Afin de distinguer les immigrants de première génération des individus nés à Québec et de discuter de l’identité des immigrants de cette ville aux XVIIIe et XIXe siècles, trente-quatre squelettes humains exhumés du cimetière protestant Saint-Matthew (Québec, 1771-1860) ont fait l’objet d’analyses ostéologiques et isotopiques du strontium (87Sr/86Sr) et de l’oxygène (δ18O). Les teneurs obtenues, bien que moins précises que les données historiques, ont permis de distinguer trois groupes d’origine, soit les individus nés à Québec (N = 12), les immigrants de première génération provenant le plus probablement des îles Britanniques et du nord de la France (N = 19) et les immigrants de première génération dont l’origine ne peut être précisée (N = 3). De plus, l’origine écossaise de certains individus a pu être suggérée en fonction de compositions isotopiques variant entre -10,0 et -9,09 % vs VSMOW. La comparaison des groupes d’origine à des données provenant de sources historiques et d’une étude antérieure a permis de dresser un portrait de l’identité des immigrants, à la fois sur les plans populationnel et individuel. De plus, les compositions isotopiques (δ18O, 87Sr/86Sr, δ13C et δ15N) nous laissent croire qu’au moins un individu pourrait être d’origine amérindienne et qu’un autre proviendrait d’une partie de l’Europe plus appauvrie en 18O (possiblement un pays scandinave ou une région alpine). La distribution spatiale des sépultures nous a également permis d’émettre des hypothèses sur les liens familiaux et sociaux d’immigrants inhumés en caveaux ou entassés de façon particulièrement modeste.

Singlet Oxygen in Microporous Silica Xerogel:Quantum Yield and Oxidation at the Gas–Solid Interface

The quantum yields of singlet oxygen production and lifetimes at the gas–solid interface in silica gel material are determined. Different photosensitizers (PS) are encapsulated in parallelepipedic xerogel monoliths (PS-SG). PS were chosen according to their known photooxidation properties: 9,10-dicyanoanthracene (DCA), 9,10-anthraquinone (ANT), and a benzophenone derivative, 4-benzoyl benzoic acid (4BB). These experiments are mainly based on time-resolved 1O2 phosphorescence detection, and the obtained FD and tD values are compared with those of a reference sensitizer for production, 1H-phenalen-1- one (PN), included in the same xerogel. The trend between their ability to oxidize organic pollutants in the gas phase and their efficiency for production is investigated through photooxidation experiments of a test pollutant dimethylsulfide (DMS). The FD value is high for DCA-SG relative to the PN reference, whereas it is slightly lower for 4BB-SG and for ANT-SG. FD is related to the production of sulfoxide and sulfone as the main oxidation products for DMS photosensitized oxidation. Additional mechanisms, leading to C!S bond cleaveage, appear to mainly occur for the less efficient singlet oxygen sensitizers 4BB-SG and ANTSG.