Suppressing magnetization exchange effects in stimulated-echo diffusion experiments

AbstractExchange of nuclear magnetization between spin pools, either by chemical exchange or by cross-relaxation or both, has a significant influence on the signal attenuation in stimulated-echo-type pulsed field gradient experiments. Hence, in such cases the obtained molecular self-diffusion coefficients can carry a large systematic error. We propose a modified stimulated echo pulse sequence that contains T2-filters during the z-magnetization store period. We demonstrate, using a common theoretical description for chemical exchange and cross-relaxation, that these filters suppress the effects of exchange on the diffusional decay in that frequent case where one of the participating spin pools is immobile and exhibits a short T2. We demonstrate the performance of this experiment in an agarose/water gel. We posit that this new experiment has advantages over other approaches hitherto used, such as that consisting of measuring separately the magnetization exchange rate, if suitable by Goldman–Shen type experiments, and then correcting for exchange effects within the framework of a two-site exchange model. We also propose experiments based on selective decoupling and applicable in systems with no large T2 difference between the different spin pools

Glyoxalase activity in human erythrocytes and mouse lymphoma, liver and brain probed with hyperpolarized C-13-methylglyoxal

Methylglyoxal is a faulty metabolite. It is a ubiquitous by-product of glucose and amino acid metabolism that spontaneously reacts with proximal amino groups in proteins and nucleic acids, leading to impairment of their function. The glyoxalase pathway evolved early in phylogeny to bring about rapid catabolism of methylglyoxal, and an understanding of the role of methylglyoxal and the glyoxalases in many diseases is beginning to emerge. Metabolic processing of methylglyoxal is very rapid in vivo and thus notoriously difficult to detect and quantify. Here we show that 13C nuclei in labeled methylglyoxal can be hyperpolarized using dynamic nuclear polarization, providing 13C nuclear magnetic resonance signal enhancements in the solution state close to 5,000-fold. We demonstrate the applications of this probe of metabolism for kinetic characterization of the glyoxalase system in isolated cells as well as mouse brain, liver and lymphoma in vivo

Glyoxalase activity in human erythrocytes and mouse lymphoma, liver and brain probed with hyperpolarized 13C-methylglyoxal.

Methylglyoxal is a faulty metabolite. It is a ubiquitous by-product of glucose and amino acid metabolism that spontaneously reacts with proximal amino groups in proteins and nucleic acids, leading to impairment of their function. The glyoxalase pathway evolved early in phylogeny to bring about rapid catabolism of methylglyoxal, and an understanding of the role of methylglyoxal and the glyoxalases in many diseases is beginning to emerge. Metabolic processing of methylglyoxal is very rapid in vivo and thus notoriously difficult to detect and quantify. Here we show that 13C nuclei in labeled methylglyoxal can be hyperpolarized using dynamic nuclear polarization, providing 13C nuclear magnetic resonance signal enhancements in the solution state close to 5,000-fold. We demonstrate the applications of this probe of metabolism for kinetic characterization of the glyoxalase system in isolated cells as well as mouse brain, liver and lymphoma in vivo

La "RMN Chromatographique"

Apparent diffusion coefficients (ADCs) can be measured by nuclear magnetic resonance (NMR) using pulsed field gradient (PFG). The addition of a chromatographic stationary phase allows decreasing selectively the solutes ADC. The sample spins at the magic angle (MAS) to average at zero the anisotropic interactions due to the sample heterogeneity. This method, that we named Chromatographic NMR, was used to apprehend the interactions near the solid phase.After the presentation of both NMR techniques (PFG and MAS), we described two methods developed to investigate the chromatographic process. In this manuscript, we showed the influence of some parameters on the ADCs measured in presence of a chromatographic stationary phase inside the rotor. These results were compared to the data obtained in HPLC. Finally, the limits and the perspectives of the method were apprehended.L’utilisation de gradients de champ magnétiques (PFG) en résonance magnétique nucléaire (RMN) permet de déterminer des coefficients de diffusion apparents (ADC). L’ajout d’une phase stationnaire est à l’origine d’un ralentissement sélectif des solutés. L’addition de ce support solide implique la mise en rotation à l’angle magique (MAS) de l’échantillon pour moyenner à zéro les interactions anisotropes. Cette méthode que nous avons appelée : RMN Chromatographique, nous a permis d’appréhender différentes interactions se produisant à proximité du support stationnaire.Après la présentation des techniques RMN utilisées (PFG et MAS), nous avons détaillé deux méthodes permettant d’investiguer les phénomènes chromatographiques. Nous avons montré l’influence d’un certains nombres de paramètres sur l’ADC en présence d’une phase stationnaire et nous avons comparé les résultats avec ceux issus de la CLHP. Enfin, les limites et les perspectives de cette méthode ont été abordées

Mathematical Modeling and Data Analysis of NMR Experiments using Hyperpolarized 13C Metabolites

Rapid-dissolution dynamic nuclear polarization (DNP) has made significant impact in the characterization and understanding of metabolism that occurs on the sub-minute timescale in several diseases. While significant efforts have been made in developing applications, and in designing rapid-imaging radiofrequency (RF) and magnetic field gradient pulse sequences, very few groups have worked on implementing realistic mathematical/kinetic/relaxation models to fit the emergent data. The critical aspects to consider when modeling DNP experiments depend on both nuclear magnetic resonance (NMR) and (bio)chemical kinetics. The former constraints are due to the relaxation of the NMR signal and the application of ‘read’ RF pulses, while the kinetic constraints include the total amount of each molecular species present. We describe the model-design strategy we have used to fit and interpret our DNP results. To our knowledge, this is the first report on a systematic analysis of DNP data

Enfin un site de production du fer chez les Gaulois du Midi : premier aperçu de l’atelier de réduction des Érables à Combaillaux (Hérault, France)

International audienceIn 2016-2017, at Combaillaux (Hérault, France), the preventive excavation carried out by the Inrap allowed the study of an exceptional set of three slag pit furnace with multiple use related to the direct iron ore reduction in 700 m2 open area. All three are based on the same model: an oblong access pit leading to a circular excavated heating chamber with a natural ventilation system activated by 5 vents arranged around the bottom of the chimney. Around the furnace, some twenty structures reflect the organization of work within the workshop. The workshop is close to several contemporary protohistoric settlements: 17 km north-east of Sextantio (Castelnau-le-Lez), 15 km north of the Gardies oppidum and 27 km from the Lattara harbour. The site would have been frequented from the beginning of the 5th century BC to the end of the 3rd century BC, but the metallurgical activity would have functioned for less than one century and would have produced between 15 and 20 tons of iron according to estimates. Today, Combaillaux Les Érables site is the oldest evidence of an iron production workshop in southern Gaul. Chemical analyses of reduction slags have revealed a specific chemical signature that can now be tracked

Enfin un site de production du fer chez les Gaulois du Midi : premier aperçu de l’atelier de réduction des Érables à Combaillaux (Hérault, France)

International audienceIn 2016-2017, at Combaillaux (Hérault, France), the preventive excavation carried out by the Inrap allowed the study of an exceptional set of three slag pit furnace with multiple use related to the direct iron ore reduction in 700 m2 open area. All three are based on the same model: an oblong access pit leading to a circular excavated heating chamber with a natural ventilation system activated by 5 vents arranged around the bottom of the chimney. Around the furnace, some twenty structures reflect the organization of work within the workshop. The workshop is close to several contemporary protohistoric settlements: 17 km north-east of Sextantio (Castelnau-le-Lez), 15 km north of the Gardies oppidum and 27 km from the Lattara harbour. The site would have been frequented from the beginning of the 5th century BC to the end of the 3rd century BC, but the metallurgical activity would have functioned for less than one century and would have produced between 15 and 20 tons of iron according to estimates. Today, Combaillaux Les Érables site is the oldest evidence of an iron production workshop in southern Gaul. Chemical analyses of reduction slags have revealed a specific chemical signature that can now be tracked

‘Chiral compartmentation’ in metabolism: Enzyme stereo-specificity yielding evolutionary options

AbstractWe introduce the concept of ‘chiral compartmentation’ in metabolism that emerges from the stereo-specificity of enzymes for their substrate(s).The fully differentiated mammalian erythrocyte has no sub-cellular organelles and yet it displays compartmentation of lactic acid that is generated either by glycolysis or the glyoxalase pathway. A form of ‘operational compartmentation’ exists, based not on the chemistry of the reactive groups in the molecules but their stereoisomerism. This we call ‘chiral compartmentation’, and the rationale for its ‘natural selection’ in the erythrocyte (and presumably in the cytoplasm of other cells) is discussed.Increasing awareness of the presence of d-amino acids in proteins in the otherwise dominant ‘l-chiral biosphere’, and of the preferential use of one enantiomer of a metabolite versus the other is largely due to recent developments in rapidly-applicable, analytical–chemical methods. We confirmed that the glyoxalase pathway yields d-lactic acid by using nuclear magnetic resonance (NMR) spectroscopy of stretched chiral hydrogels.The activities of the two lactate-producing pathways have been described by numerical integration of simultaneous non-linear differential equations, based on enzyme models like that introduced by Michaelis and Menten in 1913

MEASURING TREE WATER CONTENT AND LOCATING CONDUCTIVE TISSUES WITH PORTABLE MRI

International audienceThe use of MRI in the plant sciences has traditionally been limited due to the immobility of the devices, and restrictions with regard to sample size and shape. To overcome these limitations and to be able to study plants directly in their natural environment, we evaluated the capacities of a portable, unilateral magnet: The Nuclear Magnetic Resonance Mobile Universal Surface Explorer (NMR-MOUSE), designed by Blümich et al. [1] and commercialized by Magritek. This MRI device permits measuring the signal in increments of up to 100-micrometers, and within a depth of approximately 25-millimeters. We tested its capacity to measure tree water content by following the dehydration dynamic of cut branches from six different species and two different functional types. We also tested the device on four in-situ trees. There was a significant linear correlation between the integral of the MRI profiles obtained and the water content of the branches and trees. This significant correlation was present regardless of tree species or functional type. We then tested the capacity of the device to differentiate the conductive tissues, i.e. the xylem and phloem fluxes, within cut branches. The MRI profiles of the branches presented distinct peaks which corresponded to the xylem and phloem tissues, whose location was validated with x-ray microtomography imaging which allows the high-resolution visualization of the tissues within the sample. In conclusion, the NMR-MOUSE is a promising candidate for measuring plant water dynamics in the field