In vivo enzymatic activity of acetylCoA synthetase in skeletal muscle revealed by 13C turnover from hyperpolarized [1-13C]acetate to [1-13C]acetylcarnitine

BACKGROUND: Acetate metabolism in skeletal muscle is regulated by acetylCoA synthetase (ACS). The main function of ACS is to provide cells with acetylCoA, a key molecule for numerous metabolic pathways including fatty acid and cholesterol synthesis and the Krebs cycle. METHODS: Hyperpolarized [1-(13)C]acetate prepared via dissolution dynamic nuclear polarization was injected intravenously at different concentrations into rats. The (13)C magnetic resonance signals of [1-(13)C]acetate and [1-(13)C]acetylcarnitine were recorded in vivo for 1min. The kinetic rate constants related to the transformation of acetate into acetylcarnitine were deduced from the 3s time resolution measurements using two approaches, either mathematical modeling or relative metabolite ratios. RESULTS: Although separated by two biochemical transformations, a kinetic analysis of the (13)C label flow from [1-(13)C]acetate to [1-(13)C]acetylcarnitine led to a unique determination of the activity of ACS. The in vivo Michaelis constants for ACS were KM=0.35±0.13mM and Vmax=0.199±0.031μmol/g/min. CONCLUSIONS: The conversion rates from hyperpolarized acetate into acetylcarnitine were quantified in vivo and, although separated by two enzymatic reactions, these rates uniquely defined the activity of ACS. The conversion rates associated with ACS were obtained using two analytical approaches, both methods yielding similar results. GENERAL SIGNIFICANCE: This study demonstrates the feasibility of directly measuring ACS activity in vivo and, since the activity of ACS can be affected by various pathological states such as cancer or diabetes, the proposed method could be used to non-invasively probe metabolic signatures of ACS in diseased tissue.

U-Pb isotopic dating of fluid infiltration and metasomatism during Dalradian regional metamorphism in Connemara, western Ireland

A metasomatic diopside rock occurs at the top of the dolomitic Connemara Marble Formation of western Ireland and contains titanite and K-feldspar in addition to around 90% diopside (X(Mg) = 0.90-0.97). U-Pb isotopic measurements on this mineral assemblage show that the titanite is both unusually uranium-rich and isotopically concordant, with the result that a precise U-Pb age of 478 +/- 2.5 Ma can be determined. The age is identical within error to a less precise Rb-Sr age of diopside-K-feldspar of 483 +/- 6 Ma. Petrological evidence indicates that the assemblage crystallized at c. 620-degrees-C close to or below the closure temperature of titanite. The age thus provides a precise estimate of the time of metamorphism; this age is 11 +/- 3 Ma younger than the 490 Ma age for nearby gabbroic plutons which has previously been used to constrain the peak metamorphic age. This difference accords well with geological evidence that the gabbros were emplaced prior to the metamorphic peak. Analysis of minerals with high closure temperature from assemblages whose crystallization is unambiguously associated with a specific episode of fluid infiltration at the peak of metamorphism provides the basis for a new approach to dating metamorphism. The success of this approach is demonstrated by the results from Connemara.

New Early to Middle Triassic U-Pb ages from South China: Calibration with ammonoid biochronozones and implications for the timing of the Triassic biotic recovery

New zircon U-Pb ages are proposed for late Early and Middle Triassic volcanic ash layers from the Luolou and Baifeng formations (northwestern Guangxi, South China). These ages are based on analyses of single, thermally annealed and chemically abraded zircons. Calibration with ammonoid ages indicate a 250.6 +/- 0.5 Ma age for the early Spathian Tirolites/Columbites beds, a 248.1 +/- 0.4 Ma age for the late Spathian Neopopanoceras haugi Zone, a 246.9 +/- 0.4 Ma age for the early middle Anisian Acrochordiceras hyatti Zone, and a 244.6 +/- 0.5 Ma age for the late middle Anisian Balatonites shoshonensis Zone. The new dates and previously published U-Pb ages indicate a duration of ca. 3 my for the Spathian, and minimal durations of 4.5 +/- 0.6 my for the Early Triassic and of 6.6+0.7/-0.9 my for the Anisian. The new Spathian dates are in a better agreement with a 252.6 +/- 0.2 Ma age than with a 251.4 +/- 0.3 Ma age for the Permian-Triassic boundary. These dates also highlight the extremely uneven duration of the four Early Triassic substages (Griesbachian, Dienerian, Smithian, and Spathian), of which the Spathian exceeds half of the duration of the entire Early Triassic. The simplistic assumption of equal duration of the four Early Triassic subdivisions is no longer tenable for the reconstruction of recovery patterns following the end Permian mass extinction. (c) 2006 Elsevier B.V. All rights reserved.

Late Labradorian metamorphism and anorthosite-granitoid intrusion, Cape-Caribou River allochthon, Grenville Province, Labrador - Evidence from U-Pb geochronology

In the Cape Caribou River allochthon (CCRA), metaigneous and gneissic units occur as a shallowly plunging synform in the hanging wall of the Grand Lake thrust system (GLTS), a Grenvillian structure that forms the boundary between the Mealy Mountains and Groswater Bay terranes. The layered rocks of the CCRA are cut by a stockwork of monzonite dykes related to the Dome Mountain suite and by metadiabase-amphibolite dykes that probably form part of the ca. 1380 Ma Mealy swarm. The mafic dykes appear to postdate much of the development of subhorizontal metamorphic layering within the lower parts of the CCRA. The uppermost (least metamorphosed) units of the CCRA, the North West River anorthosite-metagabbro and the Dome Mountain monzonite suite, have been dated at 1625 +/- 6 and 1626 +/- 2 Ma, respectively. An amphibolite unit that concordantly underlies the anorthosite-metagabbro and is intruded discordantly by monzonite dykes has given metamorphic ages of 1660 +/- 3 and 1631 +/- 2 Ma. Granitoid gneisses that form the lowest level of the CCRA have given a migmatization age of 1622 +/- 6 Ma. The effects of Grenvillian metamorphism become apparent in the lower levels of the allochthon where gneisses, amphibolite, and mafic dykes have given new generation zircon ages of 1008 +/- 2, 1012 +/- 3, and 1011 +/- 3 Ma, respectively. A posttectonic pegmatite has also given zircon and monazite ages of 1016(-3)(+7) and 1013 +/- 3 Ma, respectively. Although these results indicate new growth of Grenvillian zircon, this process was generally not accompanied by penetrative deformation or melting. Thus, the formation of gneissic fabrics and the overall layered nature of the lower CCRA are a result primarily of Labradorian (1660-1620 Ma) tectonism and intrusion, and probably reflect early movement on an ancestral GLTS. Grenvillian heating and metamorphism (up to granulite facies) was strongly concentrated towards the base of the CCRA and probably occurred during northwestward thrusting of the allochthon over the Groswater Bay terrane.

U-Pb zircon dating in the middle Penninic basement of the Western Alps (Valais, Switzerland)

New ages (U-Pb isotopic data) on zircon and monazite in the pre-Alpine basement of the Penninic realm (Valais, Switzerland) are presented. They are related to a Variscan metamorphic high-grade event (ca. 330 Ma) and to post-Variscan magmatic activities (ca. 270 Ma).

Effect of chronic hypoglycaemia on glucose concentration and glycogen content in rat brain: A localized 13C NMR study.

While chronic hypoglycaemia has been reported to increase unidirectional glucose transport across the blood-brain barrier (BBB) and to increase GLUT1 expression at the endothelium, the effect on steady-state brain d-glucose and brain glycogen content is currently unknown. Brain glucose and glycogen concentrations were directly measured in vivo using localized 13C magnetic resonance spectroscopy (MRS) following 12-14 days of hypoglycaemia. Brain glucose content was significantly increased by 48%, which is consistent with an increase in the maximal glucose transport rate, Tmax, by 58% compared with the sham-treated animals. The localized 13C NMR measurements of brain glucose were directly validated by comparison with biochemically determined brain glucose content after rapid focused microwave fixation (1.4 s at 4 kW). Both in vivo MRS and biochemical measurements implied that brain glycogen content was not affected by chronic hypoglycaemia, consistent with brain glucose being a major factor controlling brain glycogen content. We conclude that the increased glucose transporter expression in chronic hypoglycaemia leads to increased brain glucose content at a given level of glycaemia. Such increased brain glucose concentrations can result in a lowered glycaemic threshold of counter-regulation observed in chronic hypoglycaemia.

U-Pb zircon dating of granitoids from the Dora-Maira massif (western Italian Alps)

Among the large number of granitic intrusions within the Dora-Maira massif, several main types can be distinguished. In this study we report field, petrographic and geochemical investigations as well as zircon typology and conventional U-Pb zircon dating of plutons representing these types. The main results are as follows: the Punta Muret augengneiss is a polymetamorphosed peraluminous granite of anatectic origin. It is 457 +/- 2 Ma old and represents one of the numerous Caledonian orthogneisses of the Alpine basement. All other dated granites are of Late Variscan age. The Cavour leucogranite is an evolved granite of probably calc-alkaline affiliation, dated at 304 +/- 2 Ma. The dioritic and granodioritic facies of the Malanaggio diorite (auct.) are typical calc-alkaline rocks, whose respective age of 290 +/- 2 and 288 +/- 2 Ma overlap within errors. The Sangone and Freidour granite types have very similar alkali-calcic characteristics; their ages are poorly constrained between 267-279 and 268-283 Ma, respectively. The new data for the Dora-Maira granites are in keeping with models of the overall evolution of the Late- to Post-Variscan magmatism in the Alpine area in terms of age distribution and progressive geochemical evolution towards alkaline melts. In a first approximation, granitic rocks across the Variscan belt seem to be increasingly younger towards the internal (southern) parts of the orogen. A Carboniferous, distensive Basin and Range situation is thought to be responsible for the magmatic activity. This tectonic context is comparable to the back-are opening of an active continental margin. The observed southward migration of the magmatism could be linked to the roll-back of the subducting Paleotethyan oceanic plate along the Variscan cordillera.

Structure et évolution thermique de la croûte supérieure des chaînes de subduction : approches thermologique et modélisation numérique, dans les North Cascades (U.S.A) et de la zone de faille Motagua (Guatemala)

Cette thèse cible l'étude de la structure thermique de la croûte supérieure (<10km) dans les arcs magmatiques continentaux, et son influence sur l'enregistrement thermochronologique de leur exhumation et de leur évolution topographique. Nous portons notre regard sur deux chaînes de montagne appartenant aux Cordillères Américaines : Les Cascades Nord (USA) et la zone de faille Motagua (Guatemala). L'approche utilisée est axée sur la thermochronologie (U-Th-Sm)/He sur apatite et zircon, couplée avec la modélisation numérique de la structure thermique de la croûte. Nous mettons en évidence la variabilité à la fois spatiale et temporelle du gradient géothermique, et attirons l'attention du lecteur sur l'importance de prendre en compte la multitude des processus géologiques perturbant la structure thermique dans les chaînes de type cordillère, c'est à dire formées lors de la subduction océanique sous un continent.Une nouvelle approche est ainsi développée pour étudier et contraindre la perturbation thermique autour des chambres magmatiques. Deux profiles âge-elevation (U-Th-Sm)/He sur apatite et zircon, ont été collectées 7 km au sud du batholithe de Chilliwack, Cascades Nord. Les résultats montrent une variabilité spatiale et temporelle du gradient géothermique lors de l'emplacement magmatique qui peut être contrainte et séparé de l'exhumation. Durant l'emplacement de l'intrusion, la perturbation thermique y atteint un état d'équilibre (-80-100 °C/km) qui est fonction du flux de magma et de ia distance à la source du magma, puis rejoint 40 °C/km à la fin du processus d'emplacement magmatique.Quelques nouvelles données (U-Th)/He, replacées dans une compilation des données existantes dans les Cascades Nord, indiquent une vitesse d'exhumation constante (-100 m/Ma) dans le temps et l'espace entre 35 Ma et 2 Ma, associée à un soulèvement uniforme de la chaîne contrôlé par l'emplacement de magma dans la croûte durant toute l'activité de l'arc. Par contre, après ~2 Ma, le versant humide de la chaîne est affecté par une accélération des taux d'exhumation, jusqu'à 3 km de croûte y sont érodés. Les glaciations ont un triple effet sur l'érosion de cette chaîne: (1) augmentation des vitesses d'érosion, d'exhumation et de soulèvement la où les précipitations sont suffisantes, (2) limitation de l'altitude contrôlé par la position de Γ Ε LA, (3) élargissement du versant humide et contraction du versant aride de la chaîne.Les modifications des réseaux de drainage sont des processus de surface souvent sous-estimés au profil d'événements climatiques ou tectoniques. Nous proposons une nouvelle approche couplant une analyse géomorphologique, des données thermochronologiques de basse température ((U-Th-Sm)/He sur apatite et zircon), et l'utilisation de modélisation numérique thermo-cinématique pour les mettre en évidence et les dater; nous testons cette approche sur la gorge de la Skagit river dans les North Cascades.De nouvelles données (U-Th)/He sur zircons, complétant les données existantes, montrent que le déplacement horizontal le long de la faille transformante continentale Motagua, la limite des plaques Caraïbe/Amérique du Nord, a juxtaposé un bloc froid, le bloc Maya (s.s.), contre un bloque chaud, le bloc Chortis (s.s.) originellement en position d'arc. En plus de donner des gammes d'âges thermochronologiques très différents des deux côtés de la faille, le déplacement horizontal rapide (~2 cm/a) a produit un fort échange thermique latéral, résultant en un réchauffement du côté froid et un refroidissement du côté chaud de la zone de faille de Motagua.Enfin des données (U-Th-Sm)/He sur apatite témoignent d'un refroidissement Oligocène enregistré uniquement dans la croûte supérieure de la bordure nord de la zone de faille Motagua. Nous tenterons ultérieurement de reproduire ce découplage vertical de la structure thermique par la modélisation de la formation d'un bassin transtensif et de circulation de fluides le long de la faille de Motagua. - This thesis focuses on the influence of the dynamic thermal structure of the upper crust (<10km) on the thermochronologic record of the exhumational and topographic history of magmatic continental arcs. Two mountain belts from the American Cordillera are studied: the North Cascades (USA) and the Motagua fault zone (Guatemala). I use a combined approach coupling apatite and zircon (U-Th-Sm}/He thermochronology and thermo- kinematic numerical modelling. This study highlights the temporal and spatial variability of the geothermal gradient and the importance to take into account the different geological processes that perturb the thermal structure of Cordilleran-type mountain belts (i.e. mountain belts related to oceanic subduction underneath a continent}.We integrate apatite and zircon (U-Th)/He data with numerical thermo-kinematic models to study the relative effects of magmatic and surface processes on the thermal evolution of the crust and cooling patterns in the Cenozoic North Cascades arc (Washington State, USA). Two age-elevation profiles that are located 7 km south of the well-studied Chiliiwack intrusions shows that spatial and temporal variability in geothermal gradients linked to magma emplacement can be contrained and separated from exhumation processes. During Chiliiwack batholith emplacement at -35-20 Ma, the geothermal gradient of the country rocks increased to a very high steady-state value (80-100°C/km), which is likely a function of magma flux and the distance from the magma source area. Including temporally varying geothermal gradients in the analysis allows quantifying the thermal perturbation around magmatic intrusions and retrieving a relatively simple denudation history from the data.The synthesis of new and previously published (U-Th)/He data reveals that denudation of the Northern Cascades is spatially and temporally constant at -100 m/Ma between ~32 and ~2 Ma, which likely reflects uplift due to magmatic crustal thickening since the initiation of the Cenozoic stage of the continental magmatic arc. In contrast, the humid flank of the North Cascades is affected by a ten-fold acceleration in exhumation rate at ~2 Ma, which we interpret as forced by the initiation of glaciations; around 3 km of crust have been eroded since that time. Glaciations have three distinct effects on the dynamics of this mountain range: (1) they increase erosion, exhumation and uplift rates where precipitation rates are sufficient to drive efficient glacial erosion; (2) they efficiently limit the elevation of the range; (3) they lead to widening of the humid flank and contraction of the arid flank of the belt.Drainage reorganizations constitute an important agent of landscape evolution that is often underestimated to the benefit of tectonic or climatic events. We propose a new method that integrates geomorphology, low-temperature thermochronometry (apatite and zircon {U-Th-Sm)/He), and 3D numerical thermal-kinematic modelling to detect and date drainage instability producing recent gorge incision, and apply this approach to the Skagit River Gorge, North Cascades.Two zircon (U-Th)/He age-elevation profiles sampled on both sides of the Motagua Fault Zone (MFZ), the boundary between the North American and the Caribbean plates, combined with published thermochronological data show that strike-slip displacement has juxtaposed the cold Maya block (s.s.) against the hot, arc derived, Chortis block (s.s ), producing different age patterns on both sides of the fault and short-wavelength lateral thermal exchange, resulting in recent heating of the cool side and cooling of the hot side of the MFZ.Finally, an apatite (U-Th-Sm)/He age-elevation profile records rapid cooling at -35 Ma localized only in the upper crust along the northern side of the Motagua fault zone. We will try to reproduce these data by modeling the thermal perturbation resulting from the formation of a transtensional basin and of fluid flow activity along a crustal- scale strike-slip fault.