Comparison of fast field-cycling magnetic resonance imaging methods and future perspectives

This article is based upon work from COST Action CA15209, supported by COST (European Cooperation in Science and Technology). M. Bödenler, C. Gösweiner and H. Scharfetter acknowledge the financial support by the European Commission in the frame of the H2020 Future and Emerging Technologies (FET-open) under grant agreement 665172, project ‘CONQUER’. L. de Rochefort acknowledges the France Life Imaging network (Grant ANR-11-INBS-0006) that partially funded the small animal FFC-MRI system. D.J. Lurie, L.M. Broche and P.J. Ross acknowledge funding from the European Union’s H2020 research and innovation programme under grant agreement No 668119, project ‘IDentIFY’.Peer reviewedPublisher PD

A Newly Identified Essential Complex, Dre2-Tah18, Controls Mitochondria Integrity and Cell Death after Oxidative Stress in Yeast

A mutated allele of the essential gene TAH18 was previously identified in our laboratory in a genetic screen for new proteins interacting with the DNA polymerase delta in yeast [1]. The present work shows that Tah18 plays a role in response to oxidative stress. After exposure to lethal doses of H2O2, GFP-Tah18 relocalizes to the mitochondria and controls mitochondria integrity and cell death. Dre2, an essential Fe/S cluster protein and homologue of human anti-apoptotic Ciapin1, was identified as a molecular partner of Tah18 in the absence of stress. Moreover, Ciapin1 is able to replace yeast Dre2 in vivo and physically interacts with Tah18. Our results are in favour of an oxidative stress-induced cell death in yeast that involves mitochondria and is controlled by the newly identified Dre2-Tah18 complex

Les mises en guerre de l'État

À partir de l’été 1914, les sociétés européennes paraissent brutalement saisies par la guerre et, ce faisant, saisies par l’État. C’est en son nom que des millions d’hommes vont s’affronter, sous l’uniforme, et que s’opère une gigantesque « mobilisation » des corps, des esprits et des ressources, pour reprendre le terme de l’époque toujours employé par les historiens et les historiennes. Cent ans plus tard, alors que tous les États ayant fait la guerre ont engagé de vastes programmes de commémoration, le moment semblait particulièrement opportun pour comprendre comment l’État parvient à faire la guerre et ce que la guerre fait à l’État. L’emprise de l’État est-elle immédiate, progressive, continue ou discontinue ? Connaît-elle des phases d’essoufflement, des ratés ? S’accompagne-t-elle de phénomènes parallèles de « déprise » ? Loin de toute généralité ou de toute extrapolation hasardeuse, est-il possible de repérer des formes de résistance ou d’évitement ? Interroger le processus de nationalisation des sociétés européennes, tel est l’un des enjeux de cet ouvrage pluridisciplinaire, largement ouvert dans l’espace et dans le temps autour du point de référence de 1914. Composé d’enquêtes bien circonscrites, l’ouvrage s’inscrit dans une histoire sociale de la guerre, et permet de questionner ce qui semble une évidence, au moins en France : la spectaculaire capacité de l’État à mobiliser, presque du jour au lendemain, une société tout entière.From the summer of 1914, European societies seem brutally seized by war and, as a consequence, seized by the State. In the name of the State, millions of men enrolled in the armed forces are to fight one another. Bodies, minds and resources are subjected to a gigantic "mobilization", a contemporary word still used by historians. A hundred years later, when all the warring States, as well as the States that were born from the conflict, are launching ambitious commemorative programs, the moment seems well chosen to study how the State wages war and, in return, how war transforms the State. As part of this vast topic, this international and multidisciplinary (history, political science, sociology) conference will address the invention of the War State, from the perspective of all the processes through which the event has – or does not have – an impact on the organisation, actions and conduct of the public power. The aim is to identify potential changes or limited adjustments, but always within situations of transition born from the conflict. Is the intensification of the State's hold on society immediate or gradual, continuous or discontinuous? Are there slower phases, failures? Is it paralleled with a loss of influence in other areas? Is it possible to detect forms of resistance or avoidance, while refraining from all generalizations and risky extrapolations? Questioning the process of nationalisation of European societies is one of the challenges of this multidisciplinary work, which is widely open in space and time around the 1914 key date. Composed of well-defined surveys, the book falls within a social perspective of war, and allows us to question what seems obvious, at least in France: the spectacular capacity of the State to mobilize, almost overnight, an entire society

Finding Our Way through Phenotypes

Despite a large and multifaceted effort to understand the vast landscape of phenotypic data, their current form inhibits productive data analysis. The lack of a community-wide, consensus-based, human- and machine-interpretable language for describing phenotypes and their genomic and environmental contexts is perhaps the most pressing scientific bottleneck to integration across many key fields in biology, including genomics, systems biology, development, medicine, evolution, ecology, and systematics. Here we survey the current phenomics landscape, including data resources and handling, and the progress that has been made to accurately capture relevant data descriptions for phenotypes. We present an example of the kind of integration across domains that computable phenotypes would enable, and we call upon the broader biology community, publishers, and relevant funding agencies to support efforts to surmount today's data barriers and facilitate analytical reproducibility

Finding Our Way through Phenotypes

Despite a large and multifaceted effort to understand the vast landscape of phenotypic data, their current form inhibits productive data analysis. The lack of a community-wide, consensus-based, human- and machine-interpretable language for describing phenotypes and their genomic and environmental contexts is perhaps the most pressing scientific bottleneck to integration across many key fields in biology, including genomics, systems biology, development, medicine, evolution, ecology, and systematics. Here we survey the current phenomics landscape, including data resources and handling, and the progress that has been made to accurately capture relevant data descriptions for phenotypes. We present an example of the kind of integration across domains that computable phenotypes would enable, and we call upon the broader biology community, publishers, and relevant funding agencies to support efforts to surmount today's data barriers and facilitate analytical reproducibility

Imagerie par résonance magnétique à champ cyclé in vivo

Fast Field Cycling Magnetic Resonance Imaging (FFC-MRI) has the ability to separate two key processes that both depends on the main field intensity B0. On one hand, signal acquisition and localization and on the other hand NMR relaxation, basis of MRI contrast. The equipment thus combines a standard MR scanner with a secondary system to rapidly switch the magnetic field B0 as compared to relaxation times. FFC enables to measure the evolution of NMR relaxation as a function of magnetic field B0, namely the NMR dispersion (NMRD) profile. Combining it with MRI the NMRD profile can be localized in vivo, together with the usual characterization at fixed B0. The NMRD profile of water carries information on molecular mobility in the surrounding biological tissues, and is thus another source of contrast. The objective of this PhD project was to further develop and evaluate the potential of FFC-MRI between 1 T and 2 T in a cancer model. This work required original instrumental and methodological developments to integrate FFC in MRI. First a precise measurement of magnetic field time profile was developed, as well as the compensation of eddy currents and of irreproducible transients in the secondary system. Moreover acquisition sequences with better signal to noise efficiency and applicable for longitudinal as well as transverse relaxation were implemented. Finally a kidney tumor mouse model was explored with FFC MRI.L’IRM en champ cyclé (FFC-MRI) permet de dissocier deux processus clés de l’IRM qui dépendent chacun du champ magnétique principal B0 : d’une part, la détection du signal RMN et sa localisation et d’autre part, la relaxation du signal RMN, source de contraste d’intérêt biologique et médical. Le système d’IRM en champ cyclé est la combinaison de deux appareils, l’un est un système d’imagerie RMN et l’autre permet de faire varier le champ magnétique B0 rapidement devant les temps de relaxation. Il est ainsi possible de mesurer la dispersion de la relaxation de l’eau, c’est-à-dire sa variation en fonction du champ magnétique et potentiellement de la cartographier de manière non invasive in vivo. La dispersion est une source de contraste complémentaire, étant donné le lien entre relaxation de l’eau et son environnement moléculaire dans les tissus biologiques. L’objectif de la thèse consiste à développer et évaluer le potentiel de l’IRM en champ cyclé entre 1 T et 2 T sur un modèle de cancer. Ce travail a nécessité des développements instrumentaux et méthodologiques originaux pour intégrer le champ cyclé à des séquences IRM. Les solutions proposées portent tout d’abord sur la mesure précise du champ magnétique au cours du temps, la compensation des courants de Foucault et celle des instabilités de l’alimentation du système de variation de l’intensité de B0. De plus, nous proposons des méthodes d’acquisition avec un gain en signal sur bruit, utilisables pour mesurer la relaxation transversale aussi bien que longitudinale. Enfin une exploration sur modèle animal (tumeur du rein sur souris) a été entreprise

In vivo fast field cycling magnetic resonance imaging

L’IRM en champ cyclé (FFC-MRI) permet de dissocier deux processus clés de l’IRM qui dépendent chacun du champ magnétique principal B0 : d’une part, la détection du signal RMN et sa localisation et d’autre part, la relaxation du signal RMN, source de contraste d’intérêt biologique et médical. Le système d’IRM en champ cyclé est la combinaison de deux appareils, l’un est un système d’imagerie RMN et l’autre permet de faire varier le champ magnétique B0 rapidement devant les temps de relaxation. Il est ainsi possible de mesurer la dispersion de la relaxation de l’eau, c’est-à-dire sa variation en fonction du champ magnétique et potentiellement de la cartographier de manière non invasive in vivo. La dispersion est une source de contraste complémentaire, étant donné le lien entre relaxation de l’eau et son environnement moléculaire dans les tissus biologiques. L’objectif de la thèse consiste à développer et évaluer le potentiel de l’IRM en champ cyclé entre 1 T et 2 T sur un modèle de cancer. Ce travail a nécessité des développements instrumentaux et méthodologiques originaux pour intégrer le champ cyclé à des séquences IRM. Les solutions proposées portent tout d’abord sur la mesure précise du champ magnétique au cours du temps, la compensation des courants de Foucault et celle des instabilités de l’alimentation du système de variation de l’intensité de B0. De plus, nous proposons des méthodes d’acquisition avec un gain en signal sur bruit, utilisables pour mesurer la relaxation transversale aussi bien que longitudinale. Enfin une exploration sur modèle animal (tumeur du rein sur souris) a été entreprise.Fast Field Cycling Magnetic Resonance Imaging (FFC-MRI) has the ability to separate two key processes that both depends on the main field intensity B0. On one hand, signal acquisition and localization and on the other hand NMR relaxation, basis of MRI contrast. The equipment thus combines a standard MR scanner with a secondary system to rapidly switch the magnetic field B0 as compared to relaxation times. FFC enables to measure the evolution of NMR relaxation as a function of magnetic field B0, namely the NMR dispersion (NMRD) profile. Combining it with MRI the NMRD profile can be localized in vivo, together with the usual characterization at fixed B0. The NMRD profile of water carries information on molecular mobility in the surrounding biological tissues, and is thus another source of contrast. The objective of this PhD project was to further develop and evaluate the potential of FFC-MRI between 1 T and 2 T in a cancer model. This work required original instrumental and methodological developments to integrate FFC in MRI. First a precise measurement of magnetic field time profile was developed, as well as the compensation of eddy currents and of irreproducible transients in the secondary system. Moreover acquisition sequences with better signal to noise efficiency and applicable for longitudinal as well as transverse relaxation were implemented. Finally a kidney tumor mouse model was explored with FFC MRI

Measurement of R2 dispersion profiles using Fast Field Cycling MRI

International audienceFast Field Cycling (FFC) MRI enables rapid and precise relaxometry measurements as a function of magnetic field B_\textrm0. Up to now, it was possible to measure longitudinal R_\textrm1-NMRD profiles and to generate innovative R_\textrm1-dispersive contrasts. However, the ability to measure transverse R_\textrm2-NMRD profiles has still to be investigated. Here, a spin-echo based FFC sequence is developed to measure R_\textrm2-dispersion, and is applied to ferritin and Gd-DOTA in the range 1.15 to 1.85 T. It is shown that measurements of R2 dispersion could be obtained accurately with the FFC-MRI technology

Genome Engineering-Based Analysis of Bearded Family Genes Reveals Both Functional Redundancy and a Nonessential Function in Lateral Inhibition in Drosophila

Lateral inhibition mediated by Notch receptor signaling regulates the determination of sensory organ precursor cells (SOPs) in Drosophila. The selection of SOPs from proneural cluster cells appears to rely on a negative feedback loop linking activation of the Notch receptor to downregulation of its ligand Delta within each cell. The molecular basis of this regulatory feedback mechanism is not known. Here, we have tested the role of the Bearded (Brd) family genes in this process. The Drosophila genome encodes eight Brd family members that interact with the E3 ubiquitin ligase Neuralized (Neur) and act as inhibitors of Neur-mediated Delta signaling. Genome engineering technologies were used to create specific deletions of all eight Brd family genes. We find that the Brd family genes mα, m4, and m6 encoded by the Enhancer of split Complex (E(spl)-C) are dispensable for Drosophila development and that deletion of the five Brd family genes encoded by the Brd Complex only reduces viability. However, deletion of all Brd family genes results in embryonic lethality. Additionally, the mα, m4, and m6 genes act redundantly with the other five Brd family genes to spatially restrict Notch activation in stage 5 embryos. These data reveal that the Brd family genes have an essential but redundant activity. While the activity of all eight Brd genes appears to be dispensable for SOP determination, clone border studies indicate that both the relative activity levels of Neur and Brd family members influence competition for the SOP fate during lateral inhibition. We propose that inhibition of Neur–Delta interaction by Brd family members is part of the feedback loop that underlies lateral inhibition in Drosophila

Design of a fast field-cycling magnetic resonance imaging system, characterization and methods for relaxation dispersion measurements around 1.5 T

International audienceThe dependence of the nuclear magnetic resonance relaxation rate on the magnetic field has been widely studied, in particular, in biomedical areas with the objectives to better understand the underlying microscopic mechanisms in tissues and provide biomarkers of diseases. By combining fast-field cycling (FFC) and magnetic resonance imaging (MRI), it is possible to provide localized relaxation dispersion measurements in heterogeneous systems with recent demonstrations in solutions, biological samples, human beings, and small animals. We report here the developments and performances of a device designed for small animal FFC-MRI comprising a resistive insert technology operating inside a 1.5 T MRI system. Specific measurement methods were developed to characterize the system efficiency, response time, homogeneity, stability, and compensation. By adding a non-linear element in the system and using a dual amplifier strategy, it is shown that large field offsets can be produced during relaxation periods while maintaining precise field control during detection periods. The measurement of longitudinal nuclear magnetic relaxation dispersion (NMRD) profiles in the range of 1.08 T-1.92 T is reported, essentially displaying a linear variation in this range for common MRI contrast agents. The slopes of both the longitudinal and transverse relaxation dispersion profiles at 1.5 T are measured and validated, extending the capabilities of previous approaches. The performances of a longitudinal relaxation dispersion mapping method are finally reported, opening the way to quantitative preclinical dispersion imaging studies at a high FFC-MRI field