A DGT Technique for Plutonium Bioavailability Measurements.

The toxicity of heavy metals in natural waters is strongly dependent on the local chemical environment. Assessing the bioavailability of radionuclides predicts the toxic effects to aquatic biota. The technique of diffusive gradients in thin films (DGT) is largely exploited for bioavailability measurements of trace metals in waters. However, it has not been applied for plutonium speciation measurements yet. This study investigates the use of DGT technique for plutonium bioavailability measurements in chemically different environments. We used a diffusion cell to determine the diffusion coefficients (D) of plutonium in polyacrylamide (PAM) gel and found D in the range of 2.06-2.29 × 10(-6) cm(2) s(-1). It ranged between 1.10 and 2.03 × 10(-6) cm(2) s(-1) in the presence of fulvic acid and in natural waters with low DOM. In the presence of 20 ppm of humic acid of an organic-rich soil, plutonium diffusion was hindered by a factor of 5, with a diffusion coefficient of 0.50 × 10(-6) cm(2) s(-1). We also tested commercially available DGT devices with Chelex resin for plutonium bioavailability measurements in laboratory conditions and the diffusion coefficients agreed with those from the diffusion cell experiments. These findings show that the DGT methodology can be used to investigate the bioaccumulation of the labile plutonium fraction in aquatic biota.

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.

The bioavailability of bromazepam, omeprazole and paracetamol given by nasogastric feeding tube.

AIMS: To characterize and compare the pharmacokinetic profiles of bromazepam, omeprazole and paracetamol when administered by the oral and nasogastric routes to the same healthy cohort of volunteers. METHODS: In a prospective, monocentric, randomized crossover study, eight healthy volunteers received the three drugs by the oral (OR) and nasogastric routes (NT). Sequential plasma samples were analyzed by high-performance liquid chromatography-UV, pharmacokinetic parameters (Cmax, AUC(0-infinity), t(1/2), k(e), tmax) were compared statistically, and Cmax, AUC(0-infinity) and t(max) were analyzed for bioequivalence. RESULTS: A statistically significant difference was seen in the AUC(0-infinity) of bromazepam, with nasogastric administration decreasing availability by about 25%: AUC(OR) = 2501 ng mL(-1) h; AUC(NT) = 1855 ng mL(-1) h (p < 0.05); ratio (geometric mean) = 0.74 [90% confidence interval (CI) 0.64-0.87]. However, this does not appear to be clinically relevant given the usual dosage range and the drug's half-life (approx. 30 h). A large interindividual variability in omeprazole parameters prevented any statistical conclusion from being drawn in terms of both modes of administration despite their similar average profile: AUC(OR) = 579 ng mL(-1) h; AUC(NT) = 587 ng mL(-1) h (p > 0.05); ratio (geometric mean) = 1.01 (90% CI 0.64-1.61). An extended study with a larger number of subjects may possibly provide clearer answers. The narrow 90% confidence limits of paracetamol indicate bioequivalence: AUC(OR) = 37 microg mL(-1) h; AUC(NT) = 41 microg mL(-1) h(p > 0.05); ratio (geometric mean) = 1.12 (90% CI 0.98-1.28). CONCLUSION: The results of this study show that the nasogastric route of administration does not appear to cause marked, clinically unsuitable alterations in the bioavailability of the tested drugs.

Exploring the mechanisms regulating nutrient bioavailability and lipid metabolism through a nutrigenomics approach

SUMMARY Following the complete sequencing of the human genome, the field of nutrition has begun utilizing this vast quantity of information to comprehensively explore the interactions between diet and genes. This approach, coined nutrigenomics, aims to determine the influence of common dietary ingredients on the genome, and attempts to relate the resulting different phenotypes to differences in the cellular and/or genetic response of the biological system. However, complementary to defining the biological outcomes of dietary ingredients, we must also understand the influence of the multiple factors (such as the microbiota, bile, and function of transporters) that may contribute to the bioavailability, and ultimately bioefficacy, of these ingredients. The gastrointestinal tract (GIT) is the body's foremost tissue boundary, interacting with nutrients, exogenous compounds and microbiota, and whose condition is influenced by the complex interplay between these environmental factors and genetic elements. In order to understand GIT nutrient-gene interactions, our goal was to comprehensively elucidate the region-specific gene expression underlying intestinal functions. We found important regional differences in the expression of members of the ATP-binding cassette family of transporters in the mouse intestine, suggesting that absorption of dietary compounds may vary along the GIT. Furthermore, the influence of the microbiota on host gene expression indicated that this luminal factor predominantly influences immune function and water transport throughout the GIT; however, the identification of region-specific functions suggest distinct host-bacterial interactions along the GIT. Thus, these findings reinforce that to understand nutrient bioavailability and GIT function, one must consider the physiologically distinct regions of the gut. Nutritional molecules absorbed by the enterocytes of the GIT enter circulation and will be selectively absorbed and metabolised by tissues throughout the body; however, their bioefficacy in the body will depend on the unique and shared molecular mechanisms of the various tissues. Using a nutrigenomic approach, the biological responses of the liver and hippocampus of mice fed different long chain-polyunsaturated fatty acids diets revealed tissue-specific responses. Furthermore, we identified stearoyl-CoA desaturase as a hepatic target for arachidonic acid, suggesting a potentially novel molecular mechanism that may protect against diet-induced obesity. In summary, this work begins to unveil the fundamentally important role that nutrigenomics will play in unravelling the molecular mechanisms, and those exogenous factors capable of influencing these mechanisms, that regulate the bioefficacy of nutritional molecules. RÉSUMÉ Suite au séquençage complet du génome humain, le domaine de la nutrition a commencé à utiliser cette vaste quantité d'information pour explorer de manière globale les interactions entre la nourriture et les gènes. Cette approche, appelée « nutrigenomics », a pour but de déterminer l'influence d'ingrédients couramment utilisés dans l'alimentation sur le génome, et d'essayer de relier ces différents phénotypes, ainsi révélés, à des différences de réponses cellulaires et/ou génétiques. Cependant, en plus de définir les effets biologiques d'ingrédients alimentaires, il est important de comprendre l'influence des multiples facteurs (telle que la microflore, la bile et la fonction des transporteurs) pouvant contribuer à la bio- disponibilité et par conséquent à l'efficacité de ces ingrédients. Le tractus gastro-intestinal (TGI), qui est la première barrière vers les tissus, interagit avec les nutriments, les composés exogènes et la microflore. La fonction de cet organe est influencée par les interactions complexes entre les facteurs environnementaux et les éléments génétiques. Dans le but de comprendre les interactions entre les nutriments et les gènes au niveau du TGI, notre objectif a été de décrire de manière globale l'expression génique spécifique de chaque région de l'intestin définissant leurs fonctions. Nous avons trouvé d'importantes différences régionales dans l'expression des transporteurs de la famille des « ATP-binding cassette transporter » dans l'intestin de souris, suggérant que l'absorption des composés alimentaires puisse varier le long de l'intestin. De plus, l'étude des effets de la microflore sur l'expression des gènes hôtes a indiqué que ce facteur de la lumière intestinale influence surtout la fonction immunitaire et le transport de l'eau à travers l'intestin. Cependant, l'identification des fonctions spécifiques de chaque région suggère des interactions distinctes entre l'hôte et les bactéries le long de l'intestin. Ainsi, ces résultats renforcent l'idée que la compréhension de la bio-disponibilité des nutriments, et par conséquent la fonction du TGI, doit prendre en considération les différences régionales. Les molécules nutritionnelles transportées par les entérocytes jusqu'à la circulation sanguine, sont ensuite sélectivement absorbées et métabolisées par les différents tissus de l'organisme. Cependant, leur efficacité biologique dépendra du mécanisme commun ou spécifique de chaque tissu. En utilisant une approche « nutriogenomics », nous avons pu mettre en évidence les réponses biologiques spécifiques du foie et de l'hippocampe de souris nourris avec des régimes supplémentés avec différents acides gras poly-insaturés à chaîne longue. De plus, nous avons identifié la stearoyl-CoA desaturase comme une cible hépatique pour l'acide arachidonique, suggérant un nouveau mécanisme moléculaire pouvant potentiellement protéger contre le développement de l'obésité. En résumé, ce travail a permis de dévoiler le rôle fondamental qu'une approche telle que la « nutrigenomics » peut jouer dans le décryptage des mécanismes moléculaires et de leur régulation par des facteurs exogènes, qui ensemble vont contrôler l'efficacité biologique des nutriments.

Weathering and the mobility of phosphorus in the catchments and forefields of the Rhone and Oberaar glaciers, central Switzerland: Implications for the global phosphorus cycle on glacial-interglacial timescales

In this study we evaluate the dynamics of the biophile element phosphorus (P) in the catchment and proglacial areas of the Rhone and Oberaar glaciers (central Switzerland). We analysed erosion and dissolution rates of P-containing minerals in the subglacial environment by sampling water and suspended sediment in glacier outlets during three ablation and two accumulation seasons. We also quantified biogeochemical weathering rates of detrital P in proglacial sedimentary deposits using two chronosequences of samples of fresh, suspended, material obtained from the Oberaar and Rhone water outlets, Little-Ice-Age (LIA) moraines and Younger Dryas (YD) tills in each catchment. Subglacial P weathering is mainly a physical process and detrital P represents more than 99%, of the precipitation-corrected total P denudation flux (234 and 540 kg km(-2) yr(-1) for the Rhone and Oberaar catchments, respectively). The calculated detrital P flux rates are three to almost five times higher than the world average flux. The precipitation-corrected soluble reactive P (SRP) flux corresponds to 1.88-1.99 kg km(-2) yr(-1) (Rhone) and 2.12-2.44 kg km(-2) yr(-1) (Oberaar), respectively. These fluxes are comparable to those of tropical rivers draining transport-limited, tectonically inactive weathering areas. In order to evaluate the efficiency of detrital P weathering in the Rhone and Oberaar proglacial areas, we systematically graded apatite grains extracted from the chronosequence in each catchment relative to weathering-induced changes in their surface morphologies (grades 1-4). Fresh apatite grains are heavily indented and dissolution rounded (grade 1). LIA grains from two 0-10 cm deep moraine samples show extensive dissolution etching, similar to surface grains from the YD profile (mean grades 2.7, 3.5 and 3.5, respectively). In these proglacial deposits, the weathering front deepens progressively as a function of time due to biocorrosion in the evolving acidic pedosphere, with mechanical indentations on grains acting as sites of preferential dissolution. We also measured iron-bound, organic and detrital P concentrations in the chronosequence and show that organic and iron-bound P has almost completely replaced detrital P in the top layers of the YD profiles. Detrital P weathering rates are calculated as 3 10 and 280 kg km(-2) yr(-1) for LIA moraines and 10 kg km(-2) yr(-1) for YD tills. During the first 300 years of glacial sediment exposure P dissolution rates are shown to be approximately 70 times higher than the mean global dissolved P flux from ice-free continents. After 11.6 kyr the flux is 2.5 times the global mean. These data strengthen the argument for substantial changes in the global dissolved P flux on glacial-interglacial timescales. A crude extrapolation from the data described here suggests that the global dissolved P flux may increase by 40-45% during the first few hundred years of a deglaciation phase

Exogenous mRNA delivery and bioavailability in gene transfer mediated by piggyBac transposition.

BACKGROUND: Up to now, the different uptake pathways and the subsequent intracellular trafficking of plasmid DNA have been largely explored. By contrast, the mode of internalization and the intracellular routing of an exogenous mRNA in transfected cells are poorly investigated and remain to be elucidated. The bioavailability of internalized mRNA depends on its intracellular routing and its potential accumulation in dynamic sorting sites for storage: stress granules and processing bodies. This question is of particular significance when a secure transposon-based system able to integrate a therapeutic transgene into the genome is used. Transposon vectors usually require two components: a plasmid DNA, carrying the gene of interest, and a source of transposase allowing the integration of the transgene. The principal drawback is the lasting presence of the transposase, which could remobilize the transgene once it has been inserted. Our study focused on the pharmacokinetics of the transposition process mediated by the piggyBac transposase mRNA transfection. Exogenous mRNA internalization and trafficking were investigated towards a better apprehension and fine control of the piggyBac transposase bioavailability. RESULTS: The mRNA prototype designed in this study provides a very narrow expression window of transposase, which allows high efficiency transposition with no cytotoxicity. Our data reveal that exogenous transposase mRNA enters cells by clathrin and caveolae-mediated endocytosis, before finishing in late endosomes 3 h after transfection. At this point, the mRNA is dissociated from its carrier and localized in stress granules, but not in cytoplasmic processing bodies. Some weaker signals have been observed in stress granules at 18 h and 48 h without causing prolonged production of the transposase. So, we designed an mRNA that is efficiently translated with a peak of transposase production 18 h post-transfection without additional release of the molecule. This confines the integration of the transgene in a very small time window. CONCLUSION: Our results shed light on processes of exogenous mRNA trafficking, which are crucial to estimate the mRNA bioavailability, and increase the biosafety of transgene integration mediated by transposition. This approach provides a new way for limiting the transgene copy in the genome and their remobilization by mRNA engineering and trafficking.

Development of bioreporter assays for the detection of bioavailability of long-chain alkanes based on the marine bacterium Alcanivorax borkumensis strain SK2.

Long-chain alkanes are a major component of crude oil and therefore potentially good indicators of hydrocarbon spills. Here we present a set of new bacterial bioreporters and assays that allow to detect long-chain alkanes. These reporters are based on the regulatory protein AlkS and the alkB1 promoter from Alcanivorax borkumensis SK2, a widespread alkane degrader in marine habitats. Escherichia coli cells with the reporter construct reacted strongly to octane in short-term (6 h) aqueous suspension assays but very slightly only to tetradecane, in line with what is expected from its low water solubility. In contrast, long-term assays (up to 5 days) with A. borkumensis bioreporters showed strong induction with tetradecane and crude oil. Gel-immobilized A. borkumensis reporter cells were used to demonstrate tetradecane and crude oil bioavailability at a distance from a source. Alcanivorax borkumensis bioreporters induced fivefold more rapid and more strongly when allowed physical contact with the oil phase in standing flask assays, suggesting a major contribution of adhered cells to the overall reporter signal. Using the flask assays we further demonstrated the effect of oleophilic nutrients and biosurfactants on oil availability and degradation by A. borkumensis. The fluorescence signal from flask assays could easily be captured with a normal digital camera, making such tests feasible to be carried out on, e.g. marine oil responder vessels in case of oil accidents.

Double-tagged fluorescent bacterial bioreporter for the study of polycyclic aromatic hydrocarbon diffusion and bioavailability.

Bacterial degradation of polycyclic aromatic hydrocarbons (PAHs), ubiquitous contaminants from oil and coal, is typically limited by poor accessibility of the contaminant to the bacteria. In order to measure PAH availability in complex systems, we designed a number of diffusion-based assays with a double-tagged bacterial reporter strain Burkholderia sartisoli RP037-mChe. The reporter strain is capable of mineralizing phenanthrene (PHE) and induces the expression of enhanced green fluorescent protein (eGFP) as a function of the PAH flux to the cell. At the same time, it produces a second autofluorescent protein (mCherry) in constitutive manner. Quantitative epifluorescence imaging was deployed in order to record reporter signals as a function of PAH availability. The reporter strain expressed eGFP proportionally to dosages of naphthalene or PHE in batch liquid cultures. To detect PAH diffusion from solid materials the reporter cells were embedded in 2 cm-sized agarose gel patches, and fluorescence was recorded over time for both markers as a function of distance to the PAH source. eGFP fluorescence gradients measured on known amounts of naphthalene or PHE served as calibration for quantifying PAH availability from contaminated soils. To detect reporter gene expression at even smaller diffusion distances, we mixed and immobilized cells with contaminated soils in an agarose gel. eGFP fluorescence measurements confirmed gel patch diffusion results that exposure to 2-3 mg lampblack soil gave four times higher expression than to material contaminated with 10 or 1 (mg PHE) g(-1).

Bioavailability of repeated oral administration of MDL 100,240, a dual inhibitor of angiotensin-converting enzyme and neutral endopeptidase in healthy volunteers.

BACKGROUND: MDL 100,240 (pyrido[2,1-a] [2]benzazepine-4-carboxylic acid,7-[[2-(acetylthio)-1-oxo-3-phenylpropyl]amino]-1,2,3,4,6,7,8, 12b-octahydro-6-oxo, [4S-[4alpha,7alpha(R(*)),12bbeta]]-) is a molecule possessing an inhibiting ability on both angiotensin converting enzyme (ACE) and neutral endopeptidase, the enzyme responsible for atrial natriuretic peptide (ANP) degradation. Such a dual mechanism of action presents a potential clinical interest for the treatment of hypertension and congestive heart failure. OBJECTIVES: To evaluate the bioavailability of MDL 100,240 and its accumulation over repeated oral administration, using ACE inhibition as a surrogate for plasma drug level and determining its profile after oral and i.v. administration. METHODS: First, in an open, one-period, single-dose study, the ACE inhibition profile was characterised following a 12.5 mg MDL 100,240 i.v. infusion. Second, in a three-group, parallel, randomised, double-blind study, each group of four subjects received q.d., over 8 days, 2.5, 10 or 20 mg of MDL 100,240 orally. The ACE inhibition profile was determined on day 1 and day 8. Trough plasma ACE was measured on days 2, 3 and 4. The recovery of ACE activity was monitored up to 72 h after the last dose of MDL 100,240. RESULTS: ACE inhibition profile was similar on day 1 and day 8, and trough inhibition remained unchanged after the 8 days of treatment with 10 mg or 20 mg. Following repeated 2.5-mg ingestion, trough inhibition increased from 33% to 44% after the eighth dose. The oral bioavailability of MDL 100,240 was estimated at 85%, not statistically different from 100%. The accumulation ratio at steady state was estimated at 112%. Expressing the accumulation ratio in terms of half-life, a t(1/2) of 0.31 days or 7. 5 h was estimated. CONCLUSION: MDL 100,240 (oral solution) has a good bioavailability, as estimated by ACE inhibition, and no drug accumulation seems to occur over 8 days with the 10-mg and 20-mg doses, but a slight rise in the trough level is observed with the 2. 5-mg dose.

Changes in arbuscular mycorrhizal fungal phenotypes and genotypes in response to plant species identity and phosphorus concentration.

* Arbuscular mycorrhizal fungi (AMF) are plant symbionts that improve floristic diversity and ecosystem productivity. Many AMF species are generalists with wide host ranges. Arbuscular mycorrhizal fungi individuals are heterokaryotic, and AMF populations are genetically diverse. Populations of AMF harbor two levels of genetic diversity on which selection can act, namely among individuals and within individuals. Whether environmental factors alter genetic diversity within populations is still unknown. * Here, we measured genetic changes and changes in fitness-related traits of genetically distinct AMF individuals from one field, grown with different concentrations of available phosphate or different host species. * We found significant genotype-by-environment interactions for AMF fitness traits in response to these treatments. Host identity had a strong effect on the fitness of different AMF, unearthing a specificity of response within Glomus intraradices. Arbuscular mycorrhizal fungi individuals grown in novel environments consistently showed a reduced presence of polymorphic genetic markers, providing some evidence for host or phosphate-induced genetic change in AMF. * Given that AMF individuals can form extensive hyphal networks colonizing different hosts simultaneously, contrasting habitats or soil properties may lead to evolution in the population. Local selection may alter the structure of AMF populations and maintain genetic diversity, potentially even within the hyphal network of one fungus.

Phosphorus and carbon burial during cretaceous oceanic anoxic events, links with climatic changes

According to Jenkyns (2010), oceanic anoxic events (OAE) record profound changes in the climatic and paleoceanographic state of the planet and represent major disturbances in the global carbon cycle. One of the most studied OAEs on a worldwide scale is the Cenomanian-Turonian OAE 2, which is characterized by a pronounced positive excursion in carbon-isotope records and the important accumulation of organic-rich sediments. The section at Gongzha (Tibet) and the sections at Barranca and Axaxacualco (Mexico) are located in remote parts of the Tethys, and show δ13C records, which are well correlated with those of classical Tethyan sections. Both sections, however, do not exhibit the presence of organic-rich sediments. Phosphorus Mass Accumulation Rates (PMAR) in Tibet show a pattern similar to that observed in the Tethys by Mort et al. (2007), which suggests enhanced Ρ regeneration during the OAE 2 time interval, though there is no evidence for anoxic conditions in Tibet. Ρ appears here to have been mainly driven by detrital influx and sea-level fluctuations. The sections at Barranca and Axaxacualco show that the Mexican carbonate platform persisted during this anoxic event, which allowed the evolution of platform fauna otherwise not present in Tethyan sections. The persistence of this carbonate platform close to the Caribbean Igneous Plateau, which is thought to have released bio-limiting metals, is explained by local uplift which delayed the drowning of the platform and a specific oceanic circulation that permitted the preservation of oligotrophic conditions in the area. The Coniacian-Santonian OAE (OAE3) appears to have been more dependent on local conditions than OAE2. The presence of black shales associated with OAE3 appear to have been restricted to shallow-water settings and epicontinental seas in areas located around the Atlantic Ocean. The sections at Olazagutia (Spain), and Ten Mile - Arbor Park (USA), two potential Global Boundary Stratotype Sections and Points (GSSP) sites, are devoid of organic-rich sediments and lack a δ13C positive excursion around the C-S boundary. The Gabal Ekma section (Sinai, Egypt) exhibits accumulations of organic-rich sediments, in addition to phosphorite bone beds layers, which may have been linked to an epicontinental upwelling zone and/or storm inputs. Our data suggest that OAE 3 is rarely expressed by truly anoxic conditions and seems to have been linked to local conditions rather than global paleoenvironmental change. The evidence for detrital-P being the likely cause of Ρ fluctuations during the OAEs studied here does not negate the idea that anoxia was the principal driver of these fluctuations in the western Tethys. However, an explanation is required as to why the Ρ accumulation signatures are mirrored in both oxic and anoxic sedimentary successions. 'Eustatic/climatic' and 'productivity/anoxic' models may have both operated simultaneously in different parts of the world depending on local conditions, both producing similar trends in Ρ accumulation. - Selon Jenkyns (2010), les événements anoxiques océaniques enregistrent de profonds changements dans le climat et la paléoceanographie de la planète et représente des perturbations majeures du cycle du carbone. L'un des plus étudiés à l'échelle mondiale est l'ΟΑΕ2 du Cénomanien-Turonien, qui est caractérisé par une très forte excursion positive des isotopes du carbone et une importante accumulation de sédiments riche en matière organique. La section de Gongzha (Tibet) et les sections de Barranca et Axaxcualco (Mexique) sont situées aux confins de la Téthys, et enregistrent une courbe isotopique en δ13C parfaitement corrélable avec les sections téthysiennes, mais ne montre pas d'accumulation de black shales. Le taux de phosphore en accumulation de masses (PMAR) au Tibet montre un pattern similaire observé également par Mort et al. (2007) dans la Téthys, suggérant un model de régénération du Ρ durant l'anoxie, cependant aucune conditions anoxiques régnent dans la région du Tibet. Ρ apparaît donc principalement guidé par le détritisme et les fluctuations du niveau marin. Les sections de Barranca et d'Axaxacualco montrent que la plateforme carbonatée mexicaine persiste durant cet événement anoxique, et permet le développement d'une faune de plateforme qui n'est pas présente dans les sections téthysiennes. La persistance de cette plateforme carbonatée si proche du plateau Caribéen, qui est connu pour le relâchement de métaux bio-limitant, peut être expliqué par un soulèvement tectonique local qui inhibe l'ennoiement de la plateforme et une circulation océanique spécifique qui permet la préservation de conditions oligotrophiques dans cette région. L'événement anoxique océanique du Coniacien-Santonien apparaît plus dépendant des conditions locales que pour l'ΟΑΕ2. Les black shales associés à POAE3 sont restreints aux zones situées autour de l'océan Atlantique et plus particulièrement aux eaux peu profondes et épicontinentales. Les sections d'Olazagutia (Espagne), Ten Mile Creek et Arbor Park (USA), qui sont deux potentielles sections GSSP (Sections de stratotype de limite globaux et de points), ne montre pas d'accumulation de black shales et pas de forte excursion positive en δ13C autour de la limite C-S. La section de Gabal Ekma (Sinai, Egypte) montre des accumulations de black shales, en plus des couches de phosphorites et d'accumulation d'os (« bone beds »), vraisemblablement lié à des zones active d'upwelling épicontinentale et/ou d'apport de tempêtes. Nos données suggèrent que l'OAE 3 est rarement exprimé par de vraies conditions anoxiques et semble être plus lié à des conditions plus locales que des changements paléo-environnementaux globaux, comme observés pour le Cénomanien- Turonien. Les arguments pour un modèle lié au phosphore détritique qui serait la cause des fluctuations du phosphore total durant les OAEs, n'écartent pas l'idée que l'anoxie est la principale cause de ces fluctuations dans les sections riches en matière organique de l'Ouest téthysien. Cependant une explication est nécessaire pour comprendre pourquoi la signature de l'accumulation du phosphore est semblable dans les successions sédimentaires déposées dans des conditions oxygénées et anoxiques. Les modèles « Eustatisme/Climat » et « Productivité/anoxie » ont simultanément opéré dans les différentes parties du monde dépendant de conditions locales, et ont produit des tendances similaires en accumulation de phosphore.

Extracellular superoxide dismutase is a major determinant of nitric oxide bioavailability: in vivo and ex vivo evidence from ecSOD-deficient mice.

The bioavailability of nitric oxide (NO) within the vascular wall is limited by superoxide anions (O2.-). The relevance of extracellular superoxide dismutase (ecSOD) for the detoxification of vascular O2.- is unknown. We determined the involvement of ecSOD in the control of blood pressure and endothelium-dependent responses in angiotensin II-induced hypertension and renovascular hypertension induced by the two-kidney, one-clip model in wild-type mice and mice lacking the ecSOD gene. Blood pressure was identical in sham-operated ecSOD+/+ and ecSOD-/- mice. After 6 days of angiotensin II-treatment and 2 and 4 weeks after renal artery clipping, blood pressure was significantly higher in ecSOD-/- than ecSOD+/+ mice. Recombinant ecSOD selectively decreased blood pressure in hypertensive ecSOD-/- mice, whereas ecSOD had no effect in normotensive and hypertensive ecSOD+/+ mice. Compared with sham-operated ecSOD+/+ mice, sham-operated ecSOD-/- mice exhibited attenuated acetylcholine-induced relaxations. These responses were further depressed in vessels from clipped animals. Vascular O2.-, as measured by lucigenin chemiluminescence, was higher in ecSOD-/- compared with ecSOD+/+ mice and was increased by clipping. The antioxidant tiron normalized relaxations in vessels from sham-operated and clipped ecSOD-/-, as well as from clipped ecSOD+/+ mice. In contrast, in vivo application of ecSOD selectively enhanced endothelium-dependent relaxation in vessels from ecSOD-/- mice. These data reveal that endogenous ecSOD is a major antagonistic principle to vascular O2.-, controlling blood pressure and vascular function in angiotensin II-dependent models of hypertension. ecSOD is expressed in such an abundance that even in situations of high oxidative stress no relative lack of enzyme activity occurs.

Phosphorus burial in the ocean over glacial-interglacial time scales

The role of nutrients, such as phosphorus (P), and their impact on primary productivity and the fluctuations in atmospheric CO2 over glacial-interglacial periods are intensely debated. Suggestions as to the importance of P evolved from an earlier proposal that P actively participated in changing productivity rates and therefore climate change, to most recent ones that changes in the glacial ocean inventory of phosphorus were important but not influential if compared to other macronutrients, such as nitrate. Using new data coming from a selection of ODP sites, we analyzed the distribution of oceanic P sedimentary phases and calculate reactive P burial fluxes, and we show how P burial fluxes changed over the last glacial-interglacial period at these sites. Concentrations of reactive P are generally lower during glacial times, while mass accumulation rates (MAR) of reactive P show higher variability. If we extrapolate for the analyzed sites, we may assume that in general glacial burial fluxes of reactive P are lower than those during interglacial periods by about 8%, because the lack of burial of reactive P on the glacial shelf reduced in size, was apparently not compensated by burial in other regions of the ocean. Using the calculated changes in P burial, we evaluate their possible impact on the phosphate inventory in the world oceans. Using a simple mathematical approach, we find that these changes alone could have increased the phosphate inventory of glacial ocean waters by 17-40% compared to interglacial stages. Variations in the distribution of sedimentary P phases at the investigated sites seem to indicate that at the onset of interglacial stages, shallower sites experienced an increase in reactive P concentrations, which seems to point to P-richer waters at glacial terminations. All these findings would support the Shelf-Nutrient Hypothesis, which assumes that during glacial low stands nutrients are transferred from shallow sites to deep sea with possible feedback on the carbon cycle.