Prolonged Period of Cortical Plasticity upon Redox Dysregulation in Fast-Spiking Interneurons.

BACKGROUND: Oxidative stress and the specific impairment of perisomatic gamma-aminobutyric acid circuits are hallmarks of the schizophrenic brain and its animal models. Proper maturation of these fast-spiking inhibitory interneurons normally defines critical periods of experience-dependent cortical plasticity. METHODS: Here, we linked these processes by genetically inducing a redox dysregulation restricted to such parvalbumin-positive cells and examined the impact on critical period plasticity using the visual system as a model (3-6 mice/group). RESULTS: Oxidative stress was accompanied by a significant loss of perineuronal nets, which normally enwrap mature fast-spiking cells to limit adult plasticity. Accordingly, the neocortex remained plastic even beyond the peak of its natural critical period. These effects were not seen when redox dysregulation was targeted in excitatory principal cells. CONCLUSIONS: A cell-specific regulation of redox state thus balances plasticity and stability of cortical networks. Mistimed developmental trajectories of brain plasticity may underlie, in part, the pathophysiology of mental illness. Such prolonged developmental plasticity may, in turn, offer a therapeutic opportunity for cognitive interventions targeting brain plasticity in schizophrenia.

NMR chemical shifts of the rhodopsin chromophore in the dark state and in bathorhodopsin: a hybrid QM/MM molecular dynamics study.

We investigate nuclear magnetic resonance (NMR) parameters of the rhodopsin chromophore in the dark state of the protein and in the early photointermediate bathorhodopsin via first-principles molecular dynamics simulations and NMR chemical shift calculations in a hybrid quantum/classical (QM/MM) framework. NMR parameters are particularly sensitive to structural properties and to the chemical environment, which allows us to address different questions about the retinal chromophore in situ. Our calculations show that both the 13C and the 1H NMR chemical shifts are rather insensitive to the protonation state of Glu181, an ionizable amino acid side chain located in the vicinity of the isomerizing 11-cis bond. Thus, other techniques should be better suited to establish its protonation state. The calculated chemical shifts for bathorhodopsin further support our previously published theoretical structure, which is in very good agreement with more recent X-ray data.

Redox Signaling by the RNA Polymerase III TFIIB-Related Factor Brf2.

TFIIB-related factor 2 (Brf2) is a member of the family of TFIIB-like core transcription factors. Brf2 recruits RNA polymerase (Pol) III to type III gene-external promoters, including the U6 spliceosomal RNA and selenocysteine tRNA genes. Found only in vertebrates, Brf2 has been linked to tumorigenesis but the underlying mechanisms remain elusive. We have solved crystal structures of a human Brf2-TBP complex bound to natural promoters, obtaining a detailed view of the molecular interactions occurring at Brf2-dependent Pol III promoters and highlighting the general structural and functional conservation of human Pol II and Pol III pre-initiation complexes. Surprisingly, our structural and functional studies unravel a Brf2 redox-sensing module capable of specifically regulating Pol III transcriptional output in living cells. Furthermore, we establish Brf2 as a central redox-sensing transcription factor involved in the oxidative stress pathway and provide a mechanistic model for Brf2 genetic activation in lung and breast cancer.

Redox dysregulation in schizophrenia : effect on myelination of cortical structures and connectivity

Cette thèse traite du rôle qu'un facteur de risque génétique développé chez les patients souffrant de schizophrénie, à savoir un déficit de la synthèse du glutathion, peut jouer dans les anomalies de la connectivité cérébrale trouvées chez ces patients. L'essentiel du travail a été consacré à évaluer la structure de la substance blanche dans l'ensemble du cerveau chez un modèle animal par une méthode similaire à celle utilisée en recherche clinique avec l'imagerie par résonance magnétique (IRM). Cette approche de translation inverse chez la souris knock-out de glutamate-cystéine ligase modulateur sous-unité (Gclm KO), avait l'objectif d'étudier l'effet des défenses redox déficientes sur le développement des connexions cérébrales, tout en excluant celui des facteurs non liés au génotype. Après avoir établi le protocole de recherche, l'influence d'une manipulation environnementale a également été étudiée. Pour effectuer une analyse statistique fiable des données d'IRM obtenues, nous .avons d'abord créé un atlas du cerveau de la souris afin de l'utiliser comme modèle pour une segmentation précise des différentes régions du cerveau sur les images IRM obtenues in vivo. Les données provenant de chaque région d'intérêt ont ensuite été étudiées séparément. La qualité de cette méthode a été évaluée dans une expérience de simulation pour déduire la puissance statistique réalisable dans chaque région en fonction du nombre d'animaux utilisés. Ces outils d'analyse nous ont permis d'évaluer l'intégrité de la substance blanche dans le cerveau des souris durant le développement grâce à une expérience longitudinale, en utilisant l'imagerie du tenseur de diffusion (DTI). Nous avons ainsi observé des anomalies dans les paramètres dérivés du tenseur (diffusivité et anisotropie) dans la Commissure Antérieure et le Fimbria/Fornix des souris Gclm KO, par rapport aux animaux contrôles. Ces résultats suggèrent une substance blanche endommagée dans ces régions. Dans une expérience électrophysiologique, Pascal Steullet a montré que ces anomalies ont des conséquences fonctionnelles caractérisées par une réduction de la vitesse de conduction dans les fibres nerveuses. Ces données renforcent les conclusions des analyses d'imagerie. Le mécanisme par lequel une dérégulation redox affecte la structure de la substance blanche reste encore à définir, car une analyse immunohistochimique des protéines constituantes de la couche de myéline des fibres concernées n'a pas donné de résultats concluants. Nous avons également constaté un élargissement des ventricules dans les jeunes souris Gclm KO, mais pas chez les adultes et des anomalies neurochimiques déjà connues chez ces animaux (Duarte et al. 2011), à savoir une réduction du Glutathion et une augmentation de l'acide N-acétylaspartique, de l'Alanine et du ratio Glutamine/Glutamate. Nous avons ensuite testé l'effet d'un stress environnemental supplémentaire, l'élevage en isolement social, sur le phénotype. Ce stress n'a eu aucun effet sur la structure de la substance blanche évaluée par DTI, mais a réduit la concentration de myo-Inositol et augmenté le ratio de Glutamine/Glutamate dans le cortex frontal. Nous avons aussi reproduit dans ce groupe indépendant d'animaux les effets du génotype sur le profil neurochimique, sur la taille des ventricules et aussi sur les paramètres dérivés du tenseur de diffusion dans le Fimbria/Fornix, mais pas dans la Commissure Antérieure. Nos résultats montrent qu'une dérégulation redox d'origine génétique perturbe la structure et la fonction de la substance blanche dans des régions spécifiques, causant ainsi l'élargissement des ventricules. Ces phénotypes rassemblent certaines caractéristiques neuro-anatomiques de la schizophrénie, mais les mécanismes qui en sont responsables demeurent encore inconnus. L'isolement social n'a pas d'effet sur la structure de la substance blanche évaluée par DTI, alors qu'il est prouvé qu'il affecte la maturation des oligodendrocytes. La neurochimie corticale et en particulier le rapport Glutamine/Glutamate a été affecté par le dérèglement redox ainsi que par l'isolement social. En conséquence, ce ratio représente un indice prometteur dans la recherche sur l'interaction du stress environnemental avec le déséquilibre redox dans le domaine de la schizophrénie. -- The present doctoral thesis is concerned with the role that a genetic risk factor for the development of schizophrenia, namely a deficit in Glutathione synthesis, may play in the anomalies of brain connectivity found in patients. Most of the effort was devoted to perform a whole-brain assessment of white matter structure in the Glutamate-Cysteine ligase modulatory knockout mouse model (Gclm KO) using Magnetic Resonance Imaging (MRI) techniques similar to those used in state-of-the-art clinical research. Such reverse translational approach taking brain imaging from the bedside to the bench aimed to investigate the role that deficient redox defenses may play in the development of brain connections while excluding all influencing factors beside the genotype. After establishing the protocol, the influence of further environmental manipulations was also studied. Analysis of MRI images acquired in vivo was one of the main challenges of the project. Our strategy consisted in creating an atlas of the mouse brain to use as segmentation guide and then analyze the data from each region of interest separately. The quality of the method was assessed in a simulation experiment by calculating the statistical power achievable in each brain region at different sample sizes. This analysis tool enabled us to assess white matter integrity in the mouse brain along development in a longitudinal experiment using Diffusion Tensor Imaging (DTI). We discovered anomalies in diffusivity parameters derived from the tensor in the Anterior Commissure and Fimbria/Fornix of Gclm KO mice when compared to wild-type animals, which suggest that the structure of these tracts is compromised in the KO mice. In an elegant electrophysiological experiment, Pascal Steullet has provided evidence that these anomalies have functional consequences in form of reduced conduction velocity in the concerned tracts, thus supporting the DTI findings. The mechanism by which redox dysregulation affects WM structure remains unknown, for the immunohistochemical analysis of myelin constituent proteins in the concerned tracts produced inconclusive results. Our experiments also detected an enlargement of the lateral ventricles in young but not adult Gclm KO mice and confirmed neurochemical anomalies already known to affect this animals (Duarte et al. 2011), namely a reduction in Glutathione and an increase in Glutamine/Glutamate ratio, N-acetylaspartate and Alanine. Using the same methods, we tested the effect of an additional environmental stress on the observed phenotype: rearing in social isolation had no effect on white matter structure as assessed by DTI, but it reduced the concentration of myo-Inositol and increased the Glutamine/Glutamate ratio in the frontal cortex. We could also replicate in this separate group of animals the effects of genotype on the frontal neurochemical profile, ventricular size and diffusivity parameters in the Fimbria/Fornix but not in the Anterior Commissure. Our data show that a redox dysregulation of genetic origin may disrupt white matter structure and function in specific tracts and cause a ventricular enlargement, phenotypes that resemble some neuroanatomical features of schizophrenia. The mechanism responsible remains however unknown. We have also demonstrated that environmental stress in form of social isolation does not affect white matter structure as assessed by DTI even though it is known to affect oligodendrocyte maturation. Cortical neurochemistry, and specifically the Glutamine to Glutamate balance was affected both by redox dysregulation and social isolation, and is thus a good target for further research on the interaction of redox imbalance and environmental stress in schizophrenia.

Glutathione deficit during development induces anomalies in the rat anterior cingulate GABAergic neurons: Relevance to schizophrenia.

A series of studies in schizophrenic patients report a decrease of glutathione (GSH) in prefrontal cortex (PFC) and cerebrospinal fluid, a decrease in mRNA levels for two GSH synthesizing enzymes and a deficit in parvalbumin (PV) expression in a subclass of GABA neurons in PFC. GSH is an important redox regulator, and its deficit could be responsible for cortical anomalies, particularly in regions rich in dopamine innervation. We tested in an animal model if redox imbalance (GSH deficit and excess extracellular dopamine) during postnatal development would affect PV-expressing neurons. Three populations of interneurons immunolabeled for calcium-binding proteins were analyzed quantitatively in 16-day-old rat brain sections. Treated rats showed specific reduction in parvalbumin immunoreactivity in the anterior cingulate cortex, but not for calbindin and calretinin. These results provide experimental evidence for the critical role of redox regulation in cortical development and validate this animal model used in schizophrenia research.

Oxidative potential for fine/ultrafine particles in occupational situations

Introduction : The redox properties of fine/ultrafine particles as well as nanoparticles (NP) are suggested to be important to explain their biological activity and could constitute a novel and promising metric for hazard evaluation. The acellular in vitro dithiothreitol (DTT) assay allows measuring this property. Objectives : (1) to evaluate sampling requirements for fine/ultrafine particle allowing measurement of their oxidative potential (2) to apply the methodology to occupational situations where particle from combustion sources are generated. Material and method : Sampling parameters (type of filters and loaded amount) and storage duration affecting the DTT measurements were evaluated. Based on these results, a methodological approach was defined and applied in two occupational situations where diesel and other combustion particles are present (toll station in a tunnel and mechanical yard for bus reparation). Results : Teflon filters loaded with diesel particles were found more suitable for the DTT assay, due to their better chemical inertness compared to quartz filters: after storage durations larger than 150 hours, an increased reactivity toward DTT was observed only with quartz filters. Reactivity was linearly correlated to the loaded mass until about 1000 μg/filter. Different redox reactivities were determined in both working places, with the mechanical yard presenting a higher DTT consumption rate. Discussion and conclusions : These results demonstrate the feasibility of this method to determine the oxidative potential of fine/ultrafine particles in occupational situations. We propose to include this approach for hazard assessment of work places with exposure to manufactured and other NP.

Differential contribution of mitochondria, NADPH oxidases, and glycolysis to region-specific oxidant stress in the anoxic-reoxygenated embryonic heart.

The ability of the developing myocardium to tolerate oxidative stress during early gestation is an important issue with regard to possible detrimental consequences for the fetus. In the embryonic heart, antioxidant defences are low, whereas glycolytic flux is high. The pro- and antioxidant mechanisms and their dependency on glucose metabolism remain to be explored. Isolated hearts of 4-day-old chick embryos were exposed to normoxia (30 min), anoxia (30 min), and hyperoxic reoxygenation (60 min). The time course of ROS production in the whole heart and in the atria, ventricle, and outflow tract was established using lucigenin-enhanced chemiluminescence. Cardiac rhythm, conduction, and arrhythmias were determined. The activity of superoxide dismutase, catalase, gutathione reductase, and glutathione peroxidase as well as the content of reduced and oxidized glutathione were measured. The relative contribution of the ROS-generating systems was assessed by inhibition of mitochondrial complexes I and III (rotenone and myxothiazol), NADPH oxidases (diphenylene iodonium and apocynine), and nitric oxide synthases (N-monomethyl-l-arginine and N-iminoethyl-l-ornithine). The effects of glycolysis inhibition (iodoacetate), glucose deprivation, glycogen depletion, and lactate accumulation were also investigated. In untreated hearts, ROS production peaked at 10.8 ± 3.3, 9 ± 0.8, and 4.8 ± 0.4 min (means ± SD; n = 4) of reoxygenation in the atria, ventricle, and outflow tract, respectively, and was associated with arrhythmias. Functional recovery was complete after 30-40 min. At reoxygenation, 1) the respiratory chain and NADPH oxidases were the main sources of ROS in the atria and outflow tract, respectively; 2) glucose deprivation decreased, whereas glycogen depletion increased, oxidative stress; 3) lactate worsened oxidant stress via NADPH oxidase activation; 4) glycolysis blockade enhanced ROS production; 5) no nitrosative stress was detectable; and 6) the glutathione redox cycle appeared to be a major antioxidant system. Thus, the glycolytic pathway plays a predominant role in reoxygenation-induced oxidative stress during early cardiogenesis. The relative contribution of mitochondria and extramitochondrial systems to ROS generation varies from one region to another and throughout reoxygenation.

Targeting mitochondria in the infection strategy of the hepatitis C virus.

Hepatitis C virus (HCV) infection induces a state of oxidative stress more pronounced than that observed in many other inflammatory diseases. Here, we propose a temporal sequence of events in the HCV-infected cell whereby the primary alteration consists of a release of Ca(2+) from the endoplasmic reticulum, followed by uptake into mitochondria. This ensues successive mitochondrial dysfunction leading to the generation of reactive oxygen species and a progressive metabolic adaptive response. Evidence is provided for a positive feed-back mechanism between alterations of calcium and redox homeostasis. This likely involves deregulation of the mitochondrial permeability transition and induces progressive dysfunction of cellular bioenergetics. Pathogenetic implications of the model and new opportunities for therapeutic intervention are discussed. This article is part of a Directed Issue entitled: Bioenergetic dysfunction, adaptation and therapy.

Sedimentology, geochemistry and mineralogy of the Paleocene-Eocene thermal maximum (PETM) : sediment records from Egypt, India and Spain

A gradual increase in Earth's surface temperatures marking the transition from the late Paleocene to early Eocene (55.8±0.2Ma), represents an extraordinary warming event known as Paleocene-Eocene Thermal Maximum (PETM). Both marine and continental sedimentary records during this period reveal evidences for the massive injection of isotopically light carbon. The carbon dioxide injection from multiple potential sources may have triggered the global warming. The importance of the PETM studies is due to the fact that the PETM bears some striking resemblances to the human-caused climate change unfolding today. Most notably, the culprit behind it was a massive injection of heat-trapping greenhouse gases into the atmosphere and oceans, comparable in volume to what our persistent burning of fossil fuels could deliver in coming centuries. The exact knowledge of what went on during the PETM could help us to foresee the future climate change. The response of the oceanic and continental environments to the PETM is different. Many factors might control the response of the environments to the PETM such as paleogeography, paleotopography, paleoenvironment, and paleodepth. To better understand the mechanisms triggering PETM events, two different environments were studied: 1) shallow marine to inner shelf environment (Wadi Nukhul, Sinai; and the Dababiya GSSP, Luxor, Egypt), and 2) terrestrial environments (northwestern India lignite mines) representing wetland, and fluvial environments (Esplugafreda, Spain) both highlighting the climatic changes observed in continental conditions. In the marine realm, the PETM is characterized by negative ö13Ccar and ô13Corg excursions and shifts in Ô15N to ~0%o values above the P/E boundary and persisting along the interval suggesting a bloom and high production of atmospheric N2-fixers. Decrease in carbonate contents could be due to dissolution and/or dilution by increasing detrital input. High Ti, K and Zr and decreased Si contents at the P/E boundary indicate high weathering index (CIA), which coincides with significant kaolinite input and suggests intense chemical weathering under humid conditions at the beginning of the PETM. Two anoxic intervals are observed along the PETM. The lower one may be linked to methane released from the continental shelf with no change in the redox proxies, where the upper anoxic to euxinic conditions are revealed by increasing U, Mo, V, Fe and the presence of small size pyrite framboids (2-5fim). Productivity sensitive elements (Cu, Ni, and Cd) show their maximum concentrated within the upper anoxic interval suggesting high productivity in surface water. The obtained data highlight that intense weathering and subsequent nutrient inputs are crucial parameters in the chain of the PETM events, triggering productivity during the recovery phase. In the terrestrial environments, the establishment of wetland conditions and consequence continental climatic shift towards more humid conditions led to migration of modern mammals northward following the extension of the tropical belts. Relative ages of this mammal event based on bio-chemo- and paleomagnetic stratigraphy support a migration path originating from Asia into Europe and North America, followed by later migration from Asia into India and suggests a barrier to migration that is likely linked to the timing of the India-Asia collision. In contrast, at Esplugafereda, northeastern Spain, the terrestrial environment reacted differently. Two significant S13C shifts with the lower one linked to the PETM and the upper corresponding to the Early Eocene Thermal Maximum (ETM2); 180/160 paleothermometry performed on two different soil carbonate nodule reveal a temperature increase of around 8°C during the PETM. The prominent increase in kaolinite content within the PETM is linked to increased runoff and/or weathering of adjacent and coeval soils. These results demonstrate that the PETM coincides globally with extreme climatic fluctuations and that terrestrial environments are very likely to record such climatic changes. - La transition Paléocène-Eocène (55,8±0,2 Ma) est marquée par un réchauffement extraordinaire communément appelé « Paleocene-Eocene Thermal Maximum » (PETM). Les données géochimiques caractérisant les sédiments marins et continentaux de cette période indiquent que ce réchauffement a été déclenché par une augmentation massive de CO2 lié à la déstabilisation des hydrates de méthane stockés le long des marges océaniques. L'étude des événements PETM constitue donc un bon analogue avec le réchauffement actuel. Le volume de CO2 émis durant le PETM est comparable avec le CO2 lié à l'activité actuelle humaine. La compréhension des causes du réchauffement du PETM peut être cruciale pour prévoir et évaluer les conséquences du réchauffement anthropogénique, en particulier les répercussions d'un tel réchauffement sur les domaines continentaux et océaniques. De nombreux facteurs entrent en ligne de compte dans le cas du PETM, tels que la paléogéographie, la paléotopographie et les paléoenvironnement. Pour mieux comprendre les réponses environnementales aux événements du PETM, 2 types d'environnements ont été choisis : (1) le domaine marin ouvert mais relativement peu profond (Wadi Nukhul. Sinai, Dababiya, Luxor, Egypte), (2) le milieu continental marécageux humide (mines de lignite, Inde) et fluviatile, semi-aride (Esplugafreda, Pyrénées espagnoles). Dans le domaine marin, le PETM est caractérisé par des excursions négatives du ô13Ccar et ô13Corg et un shift persistant des valeurs de 815N à ~ 0 %o indiquant une forte activité des organismes (bactéries) fixant l'azote. La diminution des carbonates observée durant le PETM peut-être due à des phénomènes de dissolution ou une augmentation des apports terrigènes. Des taux élevés en Ti, K et Zr et une diminution des montants de Si, reflétés par des valeurs des indices d'altération (CIA) qui coïncident avec une augmentation significative des apports de kaolinite impliquent une altération chimique accrue, du fait de conditions plus humides au début du PETM. Deux événements anoxiques globaux ont été mis en évidence durant le PETM. Le premier, situé dans la partie inférieur du PETM, serait lié à la libération des hydrates de méthane stockés le long des talus continentaux et ne correspond pas à des variations significatives des éléments sensibles aux changements de conditions redox. Le second est caractérisé par une augmentation des éléments U, Mo, V et Fe et la présence de petit framboids de pyrite dont la taille varie entre 2 et 5pm. Le second épisode anoxique est caractérisé par une forte augmentation des éléments sensibles aux changements de la productivité (Cu, Ni et Co), indiquant une augmentation de la productivité dans les eaux de surface. Les données obtenues mettent en évidence le rôle crucial joué par l'altération et les apports en nutriments qui en découlent. Ces paramètres sont cruciaux pour la succession des événements qui ont conduit au PETM, et plus particulièrement l'augmentation de la productivité dans la phase de récupération. Durant le PETM, le milieu continental est caractérisé par l'établissement de conditions humides qui ont facilité voir provoqué la migration des mammifères modernes qui ont suivi le déplacement de ces ceintures climatiques. L'âge de cette migration est basé sur des arguments chimiostratigraphiques (isotopes stables), biostratigraphiques et paléomagnétiques. Les données bibliographiques ainsi que celles que nous avons récoltées en Inde, montrent que les mammifères modernes ont d'abord migré depuis l'Asie vers l'Europe, puis dans le continent Nord américain. Ces derniers ne sont arrivés en Inde que plus tardivement, suggérant que le temps de leur migration est lié à la collision Inde-Asie. Dans le Nord-Est de l'Espagne (Esplugafreda), la réponse du milieu continental aux événements PETM est assez différente. Comme en Inde, deux excursions signicatives en ô13C ont été observées. La première correspond au PETM et la seconde est corrélée avec l'optimum thermique de l'Eocène précoce (ETM2). Les isotopes stables de l'oxygène mesurés 2 différents types de nodules calcaires provenant de paléosols suggère une augmentation de 10°C pendant le PETM. Une augmentation simultanée des taux de kaolinite indique une intensification de l'altération chimique et/ou de l'érosion de sols adjacents. Ces résultats démontrent que le PETM coïncide globalement avec des variations climatiques extrêmes qui sont très aisément reconnaissables dans les dépôts continentaux.

Trace-element and phosphorus contents in sediment associated with Cretaceous oceanic anoxic events

ABSTRACT : During my SNSF-funded Ph.D. thesis project, I studied the evolution of redox conditions and organic-carbon preservation in the western Tethyan realm during three major positive excursions in the Cretaceous δ13C record, corresponding to the Valanginian, Early Aptian and Late Cenomanian. These periods were characterized by important global environmental and climate change, which was associated with perturbations in the carbon cycle. For the period of the Valanginian δ13C excursion, total organic carbon (TOC) contents and the quality of preserved organic matter are typical of oxic pelagic settings in the western Tethys. This is confirmed by the absence of major excursions in the stratigraphic distribution of RSTE during the δ13C shift. Published TOC data from other parts of the Valanginian oceans indicate that dys- to anaerobic zones were restricted to marginal seas within the Atlantic and Southern Ocean, and to the Pacific. Phosphorus (P) and mineralogical contents suggest a stepwise climatic evolution during the Valanginian, with a humid and warm climate prior to the δ13C shift leading to an increase in continental runoff. During the δ13C shift, a decrease in detrital input and P contents suggests a change in the climate towards more and conditions. During the early Aptian oceanic anoxic event (OAE 1a), a general increase followed by a rapid decrease in P contents suggests enhanced nutrient input at the beginning of OAE 1a. The return to lower values during OAE 1 a, associated with an increase in RSTE contents, may have been related to the weakened capacity to retain P in the sedimentary reservoir due to bottom-water oxygen depletion. In basinal settings, the RSTE distribution indicates well-developed anoxic conditions during OAE la, whereas in the shallower-water environments, conditions were oxic to suboxic, rather than anoxic. Furthermore, in the deeper part of the Tethys, two distinct enrichments have been observed, indicating fluctuations in the intensity of water column anoxia during the δ73C excursion. We also studied the effect of the end-Cenomanian oceanic anoxic event (OAE 2) on an expanded section in the Chrummflueschlucht (E of Euthal, Ct Switzerland). The goal here was to identify paleoceanographic and paleoenvironmental conditions during OAE 2 in this part of the northern Tethyan margin. The results show that this section is one of the most complete sections for the Cenomanian-Turonian boundary interval known from the Helvetic realm, despite a small hiatus between sediments corresponding to peaks 1 and 2 in the δ13C record. The evolution of P contents points to an increase in the input of this nutrient at the onset of OAE 2. The trends in RSTE contents show, however, that this part of the Helvetic realm was not affected by a strong depletion in oxygen conditions during OAE 2, despite its hemipelagic position. A further goal of this project was to submit the samples to a total extraction method (a combined HF/HNO3/HCI acid digestion) and compare the results obtained by the partial HNO3 acid extraction in order to standardize the analytical prócedures in the extraction of RSTE. The obtained results for samples of OAE 1 a suggest that RSTE trends using the partial HNO3 digestion are very comparable to those obtained by the total digestion method and subsequently normalized with regards to AI contents. RÉSUMÉ : Durant ce projet de thèse, financé par le Swiss National Science Funding (SNSF), j'ai étudié l'évolution des conditions redox et de la préservation de carbone organique dans le domnaine ouesttéthysien pendant trois excursions majeures du δ13C au Crétacé correspondant au Valanginien, à l'Aptien inférieur et à la limite Cénomanien-Turonien. Ces périodes sont caractérisées par des changements climatiques et environnementaux globaux associés à des perturbations dans le cylce du carbone. Pour L'excursion positive en δ13C du Valanginien, les analyses du carbone organique total (COT) et les observations palynologiques du domaine téthysien ont présenté des indications d'environnement pélagique relativementbienoxygéné. L'absence d'enrichissements en éléments traces sensibles aux conditions redox (TE) pendant l'excursion positive en δ13C confirme ces interprétations. Les données publiées de COT dans d'autres partie du globe indiquent cependant l'existence de conditions dys- à anaérobiques dans certains bassins restreints de l'Atlantique, l'Océan Austral et du Pacifique. L'évolution du phosphore (P) et la composition minéralogique des sédiments semblent indiquer un climat relativement chaud et humide avant l'excursion en δ13C entraînant une augmentation de l'altération continentale. Pendant le shift isotopique, une diminution des apports détritiques et du P suggèrent une transition vers des conditions plus arides. À l'Aptien Inférieur, le début de l'événement anoxique (OAE 1a) est marqué par une augmentation générale du P dans les sédiments indiquant une augmentation du niveau trophique à la base de l'excursion isotopique. Durant l'événement anoxique, les sédiments sont relativement appauvris en P. Cette diminution rapide associée à des enrichissements en TE est probablement liée à une remobilisation plus importante du P lors de la mise en place de conditions anoxiques dans les eaux de fond. Dans les environnements de bassin, le comportement des TE (enrichissements bien marqués) attestent de conditions réductrices bien marquées alors que dans les environnements moins profonds, les conditions semblent plutôt oxiques à dysoxiques. De plus, deux niveaux d'enrichissement en TE ont été observés dans la partie plus profonde de la Téthys, indiquant des fluctuations assez rapides dans l'intensité de l'anoxie de la colonne d'eau. Nous avons ensuite étudié les effets de l'événement anoxique de la fin du Cenomanien (OAE 2) dans un basin marginal de la marge nord de la Téthys avec la coupe de Chrummflueschlucht (à l'est de Euthal, Ct Schwyz). Les résultats ont montré que cette coupe présente un des enregistrements sédimentaires des plus complets de l'OAE 2 dans le domaine helvétique malgré un hiatus entre le pic 1 et 2 de l'excursion en δ13C. L'évolution du P montre une augmentation au début de l'OAE 2. Cependant, la distribution des TE indique que cette région n'a pas été affectée par des conditions réductrices trop importantes. Un second aspect de ce travail a été l'étude des différentes méthodes sur l'analyse de la distribution des TE. Des échantillons de l'OAE 1a ont été soumis à deux types d'extractions, l'une dite «totale » (attaque combinée d'acides HF/HNO3/HCI) et l'autre dite partielle » (HNO3). Les résultats obtenus suggèrent que les courbes de tendances des TE acquises par extraction partielle sont semblables à celle obtenues par extraction totale et normalisées par l'AI.

Hydrocarbon biomarkers in the Topla-Mezica zinc-lead deposits, northern Karavanke/Drau Range, Slovenia: Paleoenvironment at the site of ore formation

The Mississippi Valley-type zinc and lead deposits at Topla (250,150 metric tons (t) of ore grading 1.0 wt % Zn and 3.3 wt % Pb) and Mezica (19 million metric tons (Mt) of ore grading 5.3 wt % Pb and 2.7 wt % Zn) occur within the Middle to Upper Triassic platform carbonate rocks of the northern Karavanke/Drau Range geotectonic units of the Eastern Alps, Slovenia. The ore and host rocks of these deposits have been investigated by a combination of inorganic and organic geochemical methods to determine major, trace, and rare earth element (REE) concentrations, hydrocarbon distribution, and stable isotope ratios of carbonates, kerogen, extractable organic matter, and individual hydrocarbons. These data combined with sedimentological evidence provide insight into the paleoenvironmental conditions at the site of ore formation. The carbonate isotope composition, the REE patterns, and the distribution of hydrocarbon biomarkers (normal alkanes and steranes) suggest a marine depositional environment. At Topla, a relatively high concentration of redox sensitive trace elements (V, Mo, U) in the host dolostones and REE patterns parallel to that of the North American shale composite suggest that sediments were deposited in a reducing environment. Anoxic conditions enhanced the preservation of organic matter and resulted in relatively higher total organic carbon contents (up to 0.4 wt %). The isotopic composition of the kerogen (delta C-13(kerogon) = -29.4 to -25.0 parts per thousand, delta N-15(kerogen) = -.13.6 to 6.8 parts per thousand) suggests that marine algae and/or bacteria were the main source of organic carbon with a very minor contribution from detrital continental plants and a varying degree of alteration. Extractable organic matter from Topla ore is generally depleted in C-13 compared to the associated kerogen, which is consistent with an indigenous source of the bitumens. The mineralization correlates with delta N-15(kerogen) values around 0 per mil, C-13 depleted kerogen, C-13 enriched n-heptadecane, and relatively high concentrations of bacteria] hydrocarbon biomarkers, indicating a high cyanobacterial biomass at the site of ore formation. Abundant dissimilatory sulfate-reducing bacteria, feeding on the cyanobacterial remains, led to accumulation of biogenic H2S in the pore water of the sediments. This biogenic H2S was mainly incorporated into sedimentary organic matter and diagenetic pyrite. Higher bacterial activity at the ore site also is indicated by specific concentration ratios of hydrocarbons, which are roughly correlated with total Pb plus Zn contents. This correlation is consistent with mixing of hydrothermal metal-rich, fluids and local bacteriogenic sulfide sulfur. The new geochemical data provide supporting evidence that Topla is a low-temperature Mississippi Valley-type deposit formed in an anoxic supratidal saline to hypersaline environment. A laminated cyanobacterial mat, with abundant sulfate-reducing bacteria was the main site of sulfate reduction.

Environmental effects of Deccan volcanism across the Cretaceous-Tertiary transition in Meghalaya, India

The Urn Sohryngkew section of Meghalaya, NE India, located 800-1000 km from the Deccan volcanic province, is one of the most complete Cretaceous-Tertiary boundary (KTB) transitions worldwide with all defining and supporting criteria present: mass extinction of planktic foraminifera, first appearance of Danian species, delta(13)C shift, Ir anomaly (12 ppb) and KTB red layer. The geochemical signature of the KTB layer indicates not only an extraterrestrial signal (Ni and all Platinum Group Elements (PGEs)) of a second impact that postdates Chicxulub, but also a significant component resulting from condensed sedimentation (P), redox fluctuations (As, Co, Fe, Pb, Zn, and to a lesser extent Ni and Cu) and volcanism. From the late Maastrichtian C29r into the early Danian, a humid climate prevailed (kaolinite: 40-60%, detrital minerals: 50-80%). During the latest Maastrichtian, periodic acid rains (carbonate dissolution; CIA index: 70-80) associated with pulsed Deccan eruptions and strong continental weathering resulted in mesotrophic waters. The resulting super-stressed environmental conditions led to the demise of nearly all planktic foraminiferal species and blooms (>95%) of the disaster opportunist Guembelitria cretacea. These data reveal that detrimental marine conditions prevailed surrounding the Deccan volcanic province during the main phase of eruptions in C29r below the KTB. Ultimately these environmental conditions led to regionally early extinctions followed by global extinctions at the KTB. (C) 2011 Elsevier B.V. All rights reserved.

Arabidopsis NPH1: a flavoprotein with the properties of a photoreceptor for phototropism.

The NPH1 gene of Arabidopsis thaliana encodes a 120-kilodalton serine-threonine protein kinase hypothesized to function as a photoreceptor for phototropism. When expressed in insect cells, the NPH1 protein is phosphorylated in response to blue light irradiation. The biochemical and photochemical properties of the photosensitive protein reflect those of the native protein in microsomal membranes. Recombinant NPH1 noncovalently binds flavin mononucleotide, a likely chromophore for light-dependent autophosphorylation. The fluorescence excitation spectrum of the recombinant protein is similar to the action spectrum for phototropism, consistent with the conclusion that NPH1 is an autophosphorylating flavoprotein photoreceptor mediating phototropic responses in higher plants.