Glutamatergic and GABAergic energy metabolism measured in the rat brain by (13) C NMR spectroscopy at 14.1 T.

Energy metabolism supports both inhibitory and excitatory neurotransmission processes. This study investigated the specific contribution of astrocytic metabolism to γ-aminobutyric acid (GABA) synthesis and inhibitory GABAergic neurotransmission that remained to be ilucidated in vivo. Therefore, we measured (13) C incorporation into brain metabolites by dynamic (13) C nuclear magnetic resonance spectroscopy at 14.1 T in rats under α-chloralose anaesthesia during infusion of [1,6-(13) C]glucose. The enhanced sensitivity at 14.1 T allowed to quantify incorporation of (13) C into the three aliphatic carbons of GABA non-invasively. Metabolic fluxes were determined with a mathematical model of brain metabolism comprising glial, glutamatergic and GABAergic compartments. GABA synthesis rate was 0.11 ± 0.01 μmol/g/min. GABA-glutamine cycle was 0.053 ± 0.003 μmol/g/min and accounted for 22 ± 1% of total neurotransmitter cycling between neurons and glia. Cerebral glucose oxidation was 0.47 ± 0.02 μmol/g/min, of which 35 ± 1% and 7 ± 1% was diverted to the glutamatergic and GABAergic tricarboxylic acid cycles, respectively. The remaining fraction of glucose oxidation was in glia, where 12 ± 1% of the TCA cycle flux was dedicated to oxidation of GABA. 16 ± 2% of glutamine synthesis was provided to GABAergic neurons. We conclude that substantial metabolic activity occurs in GABAergic neurons and that glial metabolism supports both glutamatergic and GABAergic neurons in the living rat brain. We performed (13) C NMR spectroscopy in vivo at high magnetic field (14.1 T) upon administration of [1,6-(13) C]glucose. This allowed to measure (13) C incorporation into the three aliphatic carbons of GABA in the rat brain, in addition to those of glutamate, glutamine and aspartate. These data were then modelled to determine fluxes of energy metabolism in GABAergic and glutamatergic neurons and glial cells.

Measurements of glial metabolic fluxes with C-11-acetate using positron emission and an adapted NMR-based metabolic modeling approach

Objectives: Acetate brain metabolism has the particularity to occur specifically in glial cells. Labeling studies, using acetate labeled either with 13C (NMR) or 11C (PET), are governed by the same biochemical reactions and thus follow the same mathematical principles. In this study, the objective was to adapt an NMR acetate brain metabolism model to analyse [1-11C]acetate infusion in rats. Methods: Brain acetate infusion experiments were modeled using a two-compartment model approach used in NMR.1-3 The [1-11C]acetate labeling study was done using a beta scintillator.4 The measured radioactive signal represents the time evolution of the sum of all labeled metabolites in the brain. Using a coincidence counter in parallel, an arterial input curve was measured. The 11C at position C-1 of acetate is metabolized in the first turn of the TCA cycle to the position 5 of glutamate (Figure 1A). Through the neurotransmission process, it is further transported to the position 5 of glutamine and the position 5 of neuronal glutamate. After the second turn of the TCA cycle, tracer from [1-11C]acetate (and also a part from glial [5-11C]glutamate) is transferred to glial [1-11C]glutamate and further to [1-11C]glutamine and neuronal glutamate through the neurotransmission cycle. Brain poster session: oxidative mechanisms S460 Journal of Cerebral Blood Flow & Metabolism (2009) 29, S455-S466 Results: The standard acetate two-pool PET model describes the system by a plasma pool and a tissue pool linked by rate constants. Experimental data are not fully described with only one tissue compartment (Figure 1B). The modified NMR model was fitted successfully to tissue time-activity curves from 6 single animals, by varying the glial mitochondrial fluxes and the neurotransmission flux Vnt. A glial composite rate constant Kgtg=Vgtg/[Ace]plasma was extracted. Considering an average acetate concentration in plasma of 1 mmol/g5 and the negligible additional amount injected, we found an average Vgtg = 0.08±0.02 (n = 6), in agreement with previous NMR measurements.1 The tissue time-activity curve is dominated by glial glutamate and later by glutamine (Figure 1B). Labeling of neuronal pools has a low influence, at least for the 20 mins of beta-probe acquisition. Based on the high diffusivity of CO2 across the blood-brain barrier; 11CO2 is not predominant in the total tissue curve, even if the brain CO2 pool is big compared with other metabolites, due to its strong dilution through unlabeled CO2 from neuronal metabolism and diffusion from plasma. Conclusion: The two-compartment model presented here is also able to fit data of positron emission experiments and to extract specific glial metabolic fluxes. 11C-labeled acetate presents an alternative for faster measurements of glial oxidative metabolism compared to NMR, potentially applicable to human PET imaging. However, to quantify the relative value of the TCA cycle flux compared to the transmitochondrial flux, the chemical sensitivity of NMR is required. PET and NMR are thus complementary.

Fast low-specific absorption rate B0 -mapping along projections at high field using two-dimensional radiofrequency pulses.

PURPOSE: At 7 Tesla (T), conventional static field (B0 ) projection mapping techniques, e.g., FASTMAP, FASTESTMAP, lead to elevated specific absorption rates (SAR), requiring longer total acquisition times (TA). In this work, the series of adiabatic pulses needed for slab selection in FASTMAP is replaced by a single two-dimensional radiofrequency (2D-RF) pulse to minimize TA while ensuring equal shimming performance. METHODS: Spiral gradients and 2D-RF pulses were designed to excite thin slabs in the small tip angle regime. The corresponding selection profile was characterized in phantoms and in vivo. After optimization of the shimming protocol, the spectral linewidths obtained after 2D localized shimming were compared with conventional techniques and published values from (Emir et al NMR Biomed 2012;25:152-160) in six different brain regions. RESULTS: Results on healthy volunteers show no significant difference (P > 0.5) between the spectroscopic linewidths obtained with the adiabatic (TA = 4 min) and the new low-SAR and time-efficient FASTMAP sequence (TA = 42 s). The SAR can be reduced by three orders of magnitude and TA accelerated six times without impact on the shimming performances or quality of the resulting spectra. CONCLUSION: Multidimensional pulses can be used to minimize the RF energy and time spent for automated shimming using projection mapping at high field. Magn Reson Med, 2014. © 2014 Wiley Periodicals, Inc.

The neurochemical profile quantified by in vivo 1H NMR spectroscopy.

Proton NMR spectroscopy is emerging from translational and preclinical neuroscience research as an important tool for evidence based diagnosis and therapy monitoring. It provides biomarkers that offer fingerprints of neurological disorders even in cases where a lesion is not yet observed in MR images. The collection of molecules used as cerebral biomarkers that are detectable by (1)H NMR spectroscopy define the so-called "neurochemical profile". The non-invasive quality of this technique makes it suitable not only for diagnostic purposes but also for therapy monitoring paralleling an eventual neuroprotection. The application of (1)H NMR spectroscopy in basic and translational neuroscience research is discussed here.

In vivo 13C NMR spectroscopy and metabolic modeling in the brain: a practical perspective.

In vivo 13C NMR spectroscopy has the unique capability to measure metabolic fluxes noninvasively in the brain. Quantitative measurements of metabolic fluxes require analysis of the 13C labeling time courses obtained experimentally with a metabolic model. The present work reviews the ingredients necessary for a dynamic metabolic modeling study, with particular emphasis on practical issues.

Étude des sédiments quaternaires, de la molasse et sa tectonique, dans le Grand Lac (Léman) à partir de données sismiques 2D et 3D

RESUME L'Institut de Géophysique de l'Université de Lausanne a développé au cours de ces dernières années un système d'acquisition de sismique réflexion multitrace à haute résolution 2D et 3D. L'objectif de cette thèse était de poursuivre ce développement tout améliorant les connaissances de la géologie sous le lac Léman, en étudiant en particulier la configuration des grands accidents sous-lacustres dans la Molasse (Tertiaire) qui forme l'essentiel du substratum des formations quaternaires. En configuration 2D, notre système permet d'acquérir des profils sismiques avec une distance inter-CDP de 1,25 m. La couverture varie entre 6 et 18 selon le nombre de traces et la distance inter-tir. Le canon à air (15/15 eu. in.), offre une résolution verticale de 1,25 ni et une pénétration maximale de 300 m sous le fond de l'eau. Nous avons acquis au total plus de 400 km de sections 2D dans le Grand Lac et le Haut Lac entre octobre 2000 et juillet 2004. Une campagne de sismique 3D a fourni des données au large d'Evian sur une surface de 442,5 m sur 1450 m, soit 0,64 km2. La navigation ainsi que le positionnement des hydrophones et de la source ont été réalisés avec des GPS différentiels. Nous avons utilisé un traitement sismique conventionnel, sans appliquer d'AGC et en utilisant une migration post-stack. L'interprétation du substratum antéquaternaire est basée sur l'identification des sismofaciès, sur leurs relations avec les unités géologiques adjacentes au lac, ainsi que sur quelques données de forages. Nous obtenons ainsi une carte des unités géologiques dans le Grand Lac. Nous précisons la position du chevauchement subalpin entre la ville de Lausanne, sur la rive nord, et le bassin de Sciez, sur la rive sud. Dans la Molasse de Plateau, nous avons identifié les décrochements de Pontarlier et de St. Cergue ainsi que plusieurs failles non reconnues jusqu'ici. Nous avons cartographié les accidents qui affectent la Molasse subalpine ainsi que le plan de chevauchement du flysch sur la Molasse près de la rive sud du lac. Une nouvelle carte tectonique de la région lémanique a ainsi pu être dressée. L'analyse du substratum ne montre pas de failles suggérant une origine tectonique de la cuvette lémanique. Par contre, nous suggérons que la forme du creusement glaciaire, donc de la forme du lac Léman, a été influencée par la présence de failles dans le substratum antéquaternaire. L'analyse des sédiments quaternaires nous a permis de tracer des cartes des différentes interfaces ou unités qui les composent. La carte du toit du substratum antéquaternaire montre la présence de chenaux d'origine glaciaire dont la profondeur maximale atteint la cote -200 ni. Leur pente est dirigée vers le nord-est, à l'inverse du sens d'écoulement actuel des eaux. Nous expliquons cette observation par l'existence de circulations sous-glaciaires d'eau artésienne. Les sédiments glaciaires dont l'épaisseur maximale atteint 150 ni au centre du lac ont enregistré les différentes récurrences glaciaires. Dans la zone d'Evian, nous mettons en évidence la présence de lentilles de sédiments glaciolacustres perchées sur le flanc de la cuvette lémanique. Nous avons corrélé ces unités avec des données de forage et concluons qu'il s'agit du complexe inférieur de la pile sédimentaire d'Evian. Celui-ci, âgé de plus de 30 000 ans, serait un dépôt de Kame associé à un lac périglaciaire. La sismique réflexion 3D permet de préciser l'orientation de l'alimentation en matériel détritique de l'unité. La finesse des images obtenues nous permet également d'établir quels types d'érosion ont affecté certaines unités. Les sédiments lacustres, dont l'épaisseur maximale imagée atteint plus de 225 m et sans doute 400 ni sous le delta du Rhône, indiquent plusieurs mécanismes de dépôts. A la base, une mégaturbidite, épaisse d'une trentaine de mètres en moyenne, s'étend entre l'embouchure de la Dranse et le delta du Rhône. Au-dessus, la décantation des particules en suspension d'origine biologique et détritique fournit l'essentiel des sédiments. Dans la partie orientale du lac, les apports détritiques du Rhône forment un delta qui prograde vers l'ouest en s'imbriquant avec les sédiments déposés par décantation. La structure superficielle du delta a brutalement évolué, probablement à la suite de l'évènement catastrophique du Tauredunum (563 A.D.). Sa trace probable se marque par la présence d'une surface érosive que nous avons cartographiée. Le delta a ensuite changé de géométrie, avec notamment un déplacement des chenaux sous-lacustres. Sur l'ensemble de nos sections sismiques, nous n'observons aucune faille dans les sédiments quaternaires qui attesterait d'une tectonique postglaciaire du substratum. ABSTRACT During the last few years the institute of Geophysics of the University of Lausanne cleveloped a 2D and 3D high-resolution multichannel seismic reflection acquisition system. The objective of the present work was to carry on this development white improving our knowledge of the geology under Lake Geneva, in particular by studying the configuration of the large accidents affecting the Tertiary Molasse that makes up the basement of most Quaternary deposits. In its 2D configuration, our system makes it possible to acquire seismic profiles with a CDP interval of 1.25 m. The fold varies from 6 to 18 depending on the number of traces and the shooting interval. Our air gun (15/15 cu. in.) provides a vertical resolution of 1.25 m and a maximum penetration depth of approximately 300 m under water bottom. We acquired more than 400 km of 2D sections in the Grand Lac and the Haut Lac between October 2000 and July 2004. A 3D seismic survey off the city of Evian provided data on a surface of 442.5 m x 1450 m (0.64 km2). Ship's navigation as well as hydrophone- and source positioning were carried out with differential GPS. The seismic data were processed following a conventional sequence without .applying AGC and using post-stack migration. The interpretation of the pre-Quaternary substratum is based on sismofacies, on their relationships with terrestrial geological units and on some borehole data. We thus obtained a map of the geological units in the Grand Lac. We defined the location of the subalpine thrust from Lausanne, on the north shore, to the Sciez Basin, on the south shore. Within the Molasse de Plateau, we identified the already know Pontarlier and St Cergue transforms Fault as well as faults. We mapped faults that affect subalpine Molasse as well as the thrust fault plane between alpine flysch and Molasse near the lake's south shore. A new tectonic map of the Lake Geneva region could thus be drawn up. The substratum does not show faults indicating a tectonic origin for the Lake Geneva Basin. However, we suggest that the orientation of glacial erosion, and thus the shape of Lake Geneva, vas influenced by the presence of faults in the pre-Quaternary basement. The analysis of Quaternary sediments enabled us to draw up maps of various discontinuities or internal units. The top pre-Quaternary basement map shows channels of glacial origin, the deepest of them reaching an altitude of 200 m a.s.l. The channel's slopes are directed to the North-East, in opposite direction of the present water flow. We explain this observation by the presence of artesian subglacial water circulation. Glacial sediments, the maximum thickness of which reaches 150 m in the central part of the lake, record several glacial recurrences. In the Evian area, we found lenses of glacio-lacustrine sediments set high up on the flank of the Lake Geneva Bassin. We correlated these units with on-land borehole data and concluded that they represent the lower complex of the Evian sedimentary pile. The lower complex is aider than 30 000 years, and it could be a Kame deposit associated with a periglacial lake. Our 3D seismic reflexion survey enables us to specify the supply direction of detrital material in this unit. With detailed seismic images we established how some units were affected by different erosion types. The lacustrine sediments we imaged in Lake Geneva are thicker than 225 m and 400 m or more Linder the Rhone Delta. They indicate several depositional mechanisms. Their base is a major turbidite, thirty meters thick on average, that spreads between the Dranse mouth and the Rhone delta. Above this unit, settling of suspended biological and detrital particles provides most of the sediments. In the eastern part of the lake, detrital contribution from the Rhone builds a delta that progrades to the west and imbricates with the settling sediments. The shallow structure of the Rhone delta abruptly evolved, probably after the catastrophic Tauredunum event (563 A.D.). It probably coincides with an erosive surface that we mapped. As a result, the delta geometry changed, in particular associated with a displacement of water bottom channels. In all our seismic sections, we do not observe fault in the Quaternary sediments that would attest postglacial tectonic activity in the basement.

Proton NMR of (15)N-choline metabolites enhanced by dynamic nuclear polarization.

Chemical shifts of protons can report on metabolic transformations such as the conversion of choline to phosphocholine. To follow such processes in vivo, magnetization can be enhanced by dynamic nuclear polarization (DNP). We have hyperpolarized in this manner nitrogen-15 spins in (15)N-labeled choline up to 3.3% by irradiating the 94 GHz electron spin resonance of admixed TEMPO nitroxide radicals in a magnetic field of 3.35 T during ca. 3 h at 1.2 K. The sample was subsequently transferred to a high-resolution magnet, and the enhanced polarization was converted from (15)N to methyl- and methylene protons, using the small (2,3)J((1)H,(15)N) couplings in choline. The room-temperature lifetime of nitrogen polarization in choline, T(1)((15)N) approximately 200 s, could be considerably increased by partial deuteration of the molecule. This procedure enables studies of choline metabolites in vitro and in vivo using DNP-enhanced proton NMR.

Selective resonance suppression 1H-[13C] NMR spectroscopy with asymmetric adiabatic RF pulses.

Despite obvious improvements in spectral resolution at high magnetic field, the detection of 13C labeling by 1H-[13C] NMR spectroscopy remains hampered by spectral overlap, such as in the spectral region of 1H resonances bound to C3 of glutamate (Glu) and glutamine (Gln), and C6 of N-acetylaspartate (NAA). The aim of this study was to develop, implement, and apply a novel 1H-[13C] NMR spectroscopic editing scheme, dubbed "selective Resonance suppression by Adiabatic Carbon Editing and Decoupling single-voxel STimulated Echo Acquisition Mode" (RACED-STEAM). The sequence is based on the application of two asymmetric narrow-transition-band adiabatic RF inversion pulses at the resonance frequency of the 13C coupled to the protons that need to be suppressed during the mixing time (TM) period, alternating the inversion band downfield and upfield from the 13C resonance on odd and even scans, respectively, thus suppressing the detection of 1H resonances bound to 13C within the transition band of the inversion pulse. The results demonstrate the efficient suppression of 1H resonances bound to C3 of Glu and Gln, and C4 of Glu, which allows the 1H resonances bound to C6 of NAA and C4 of Gln to be revealed. The measured time course of the resolved labeling into NAA C6 with the new scheme was consistent with the slow turnover of NAA.

Desenvolupament d'un motor 2D per videojocs de plataformes mòbils

L’objectiu del projecte és la creació d’un motor gràfic id’esdeveniments per a jocs RPG per a plataformes mòbils, en aquest casper a Nintendo DS. S’ha de remarcar que el que s’està proposant no és laprogramació d’un videojoc, sinó que el que es desenvoluparà és el motorde joc. Aquest motor comptarà no solament amb la funcionalitat bàsica devisualització i animació d’escenaris i personatges, detecció de col•lisionsentre personatges i elements de l’escenari, sinó que a més, comptarà ambles funcionalitats pròpies dels jocs més sofisticats (esdeveniments). Aquestmotor és compatible per a Nintendo DS i/o qualsevol emulador d’aquestaplataforma per a PC

Fetal testosterone (2D:4D) as predictor of cognitive reflection

The Cognitive Reflection Test (CRT) is a test introduced by S. Frederick (2005) Cognitive reflection and decision making, J Econ Perspect 19(4): 25-42. The task is designed to measure the tendency to override an intuitive response that is incorrect and to engage in further reflection that leads to the correct response. The consistent sex differences in CRT performance may suggest a role for gonadal hormones, particularly testosterone. A now widely studied putative marker for fetal testosterone is the second-to-fourth digit ratio (2D:4D). This paper tests to what extent 2D:4D, as a proxy for prenatal exposure to testosterone, can predict CRT scores in a sample of 623 students. After controlling for sex, we observe that a lower 2D:4D (reflecting a higher exposure to testosterone) is significantly associated with a higher number of correct answers. The result holds for both hands? 2D:4Ds. In addition, the effect appears to be sharper for females than for males. We also control for patience and math proficiency, which are significantly related to performance in the CRT. But the effect of 2D:4D on performance in CRT is not reduced with these controls, implying that these variables are not mediating the relationship between digit ratio and CRT.

Three-Dimensional (3D) Microarchitecture Correlations with 2D Projection Image Gray-Level Variations Assessed by Trabecular Bone Score Using High-Resolution Computed Tomographic Acquisitions: Effects of Resolution and Noise.

The aim of the present study is to determine the level of correlation between the 3-dimensional (3D) characteristics of trabecular bone microarchitecture, as evaluated using microcomputed tomography (μCT) reconstruction, and trabecular bone score (TBS), as evaluated using 2D projection images directly derived from 3D μCT reconstruction (TBSμCT). Moreover, we have evaluated the effects of image degradation (resolution and noise) and X-ray energy of projection on these correlations. Thirty human cadaveric vertebrae were acquired on a microscanner at an isotropic resolution of 93μm. The 3D microarchitecture parameters were obtained using MicroView (GE Healthcare, Wauwatosa, MI). The 2D projections of these 3D models were generated using the Beer-Lambert law at different X-ray energies. Degradation of image resolution was simulated (from 93 to 1488μm). Relationships between 3D microarchitecture parameters and TBSμCT at different resolutions were evaluated using linear regression analysis. Significant correlations were observed between TBSμCT and 3D microarchitecture parameters, regardless of the resolution. Correlations were detected that were strongly to intermediately positive for connectivity density (0.711≤r(2)≤0.752) and trabecular number (0.584≤r(2)≤0.648) and negative for trabecular space (-0.407 ≤r(2)≤-0.491), up to a pixel size of 1023μm. In addition, TBSμCT values were strongly correlated between each other (0.77≤r(2)≤0.96). Study results show that the correlations between TBSμCT at 93μm and 3D microarchitecture parameters are weakly impacted by the degradation of image resolution and the presence of noise.

Screening for wound-induced oxylipins in Arabidopsis thaliana by differential HPLC-APCI/MS profiling of crude leaf extracts and subsequent characterisation by capillary-scale NMR

A simple non-targeted differential HPLC-APCI/MS approach has been developed in order to survey metabolome modifications that occur in the leaves of Arabidopsis thaliana following wound-induced stress. The wound-induced accumulation of metabolites, particularly oxylipins, was evaluated by HPLC-MS analysis of crude leaf extracts. A generic, rapid and reproducible pressure liquid extraction procedure was developed for the analysis of restricted leaf samples without the need for specific sample preparation. The presence of various oxylipins was determined by head-to-head comparison of the HPLC-MS data, filtered with a component detection algorithm, and automatically compared with the aid of software searching for small differences in similar HPLC-MS profiles. Repeatability was verified in several specimens belonging to different series. Wound-inducible jasmonates were efficiently highlighted by this non-targeted approach without the need for complex sample preparation as is the case for the 'oxylipin signature' procedure based on GC-MS. Furthermore this HPLC-MS screening technique allowed the isolation of induced compounds for further characterisation by capillary-scale NMR (CapNMR) after HPLC scale-up. In this paper, the screening method is described and applied to illustrate its potential for monitoring polar and non-polar stress-induced constituents as well as its use in combination with CapNMR for the structural assignment of wound-induced compounds of interest

Juego 2D para Android

El proyecto consistirá en diseñar desde cero un juego para smartphones que utilicen el sistema operativo Android. El objetivo del juego será sobrevivir a las oleadas de enemigos, que aparecerán en el extremo derecho de la pantalla y se dirigirán al lado opuesto, durante el tiempo suficiente para superar el nivel actual. Al mismo tiempo tendremos que tratar de esquivar los obstáculos y recoger los objetos que nos proporcionarán un bonus de puntos. En el juego habrá un número finito de niveles, cada uno más difícil que el anterior.