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1. Nigral ATP13A2 depletion induces Parkinson’s disease-related neurodegeneration in a pilot study in non-human primates

Author

Joanna Sikora, Sandra Dovero, Rémi Kinet, Marie-Laure Arotcarena, Sylvain Bohic, Erwan Bezard, Pierre-Olivier Fernagut, and Benjamin Dehay

Subjects
Neurology. Diseases of the nervous system, RC346-429
Abstract

Abstract Lysosomal impairment is strongly implicated in Parkinson’s disease (PD). Among the several PD-linked genes, the ATP13A2 gene, associated with the PARK9 locus, encodes a transmembrane lysosomal P5-type ATPase. Mutations in the ATP13A2 gene were primarily identified as the cause of Kufor-Rakeb syndrome (KRS), a juvenile-onset form of PD. Subsequently, an increasing list of several mutations has been described. These mutations result in truncation of the ATP13A2 protein, leading to a loss of function but surprisingly causing heterogeneity and variability in the clinical symptoms associated with different brain pathologies. In vitro studies show that its loss compromises lysosomal function, contributing to cell death. To understand the role of ATP13A2 dysfunction in disease, we disrupted its expression through a viral vector-based approach in nonhuman primates. Here, in this pilot study, we injected bilaterally into the substantia nigra of macaques, a lentiviral vector expressing an ATP13A2 small hairpin RNA. Animals were terminated five months later, and brains were harvested and compared with historical non-injected control brains to evaluate cerebral pathological markers known to be affected in KRS and PD. We characterised the pattern of dopaminergic loss in the striatum and the substantia nigra, the regional distribution of α-synuclein immunoreactivity in several brain structures, and its pathological status (i.e., S129 phosphorylation), the accumulation of heavy metals in nigral sections and occurrence of lysosomal dysfunction. This proof-of-concept experiment highlights the potential value of lentivirus-mediated ATP13A2 silencing to induce significant and ongoing degeneration in the nigrostriatal pathway, α-synuclein pathology, and iron accumulation in nonhuman primates.

Published
2024
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2. Nanoscintillator Coating: A Key Parameter That Strongly Impacts Internalization, Biocompatibility, and Therapeutic Efficacy in Pancreatic Cancer Models

Author

Clémentine Aubrun Fulbert, Frédéric Chaput, Sarah Stelse‐Masson, Maxime Henry, Benoit Chovelon, Sylvain Bohic, Dennis Brueckner, Jan Garrevoet, Christine Moriscot, Benoit Gallet, Julien Vollaire, Olivier Nicoud, Frédéric Lerouge, Sandrine Denis‐Quanquin, Xavier Jaurand, Thibault Jacquet, Anthony Nomezine, Véronique Josserand, Jean‐Luc Coll, Jean‐Luc Ravanat, Hélène Elleaume, and Anne‐Laure Bulin

Subjects
biocompatibility, nanoparticle functionalization, nanoscintillators, pancreatic cancer, radiation dose‐enhancement, radiotherapy, Materials of engineering and construction. Mechanics of materials, TA401-492
Abstract

Pancreatic cancer is associated with a poor prognosis despite multimodal treatments. To improve the efficacy of radiotherapy, the use of nanoscintillators is emerging. Made of high‐Z elements, they absorb X‐rays more efficiently than tissues and can locally enhance the radiation dose provided they have accumulated near tumor cells. This study focuses on the role of the coating, a key parameter that controls both in vitro and in vivo properties of nanoparticles, including their internalization, biocompatibility, and therapeutic efficacy. Polyethylene glycol and tripolyphosphate molecules are used to coat lanthanum fluoride nanoscintillators, and their properties are evaluated on pancreatic cancer models. The experiments demonstrate a higher internalization of the nanoparticles when coated with tripolyphosphate, in both 2D and 3D culture models, correlating with greater efficacy under X‐rays, which may be associated with higher radiation dose‐enhancement. The nanoparticles are also injected intravenously in healthy or tumor‐bearing mice in order to study their toxicity, pharmacokinetics, and biodistribution. Despite a strong liver and spleen accumulation, especially for the tripolyphosphate‐coated nanoparticles, no toxicity is observed for either coating. Because they show promising radiation dose‐enhancement in vitro in both culture models and a limited toxicity in vivo, polyethylene glycol‐coated nanoparticles are good candidates for biomedical applications.

Published
2024
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3. Selenium nanoparticles modulate histone methylation via lysine methyltransferase activity and S-adenosylhomocysteine depletion

Author

Benoit Toubhans, Nour Alkafri, Marcos Quintela, David W. James, Caroline Bissardon, Salvatore Gazze, Franziska Knodel, Olivier Proux, Alexandra T. Gourlan, Philipp Rathert, Sylvain Bohic, Deyarina Gonzalez, Lewis W. Francis, Laurent Charlet, and R. Steven Conlan

Subjects
Medicine (General), R5-920, Biology (General), QH301-705.5
Abstract

At physiological levels, the trace element selenium plays a key role in redox reactions through the incorporation of selenocysteine in antioxidant enzymes. Selenium has also been evaluated as a potential anti-cancer agent, where selenium nanoparticles have proven effective, and are well tolerated in vivo at doses that are toxic as soluble Se. The use of such nanoparticles, coated with either serum albumin or the naturally occurring alkaline polysaccharide chitosan, also serves to enhance biocompatibility and bioavailability. Here we demonstrate a novel role for selenium in regulating histone methylation in ovarian cancer cell models treated with inorganic selenium nanoparticles coated with serum albumin or chitosan. As well as inducing thioredoxin reductase expression, ROS activity and cancer cell cytotoxicity, coated nanoparticles caused significant increases in histone methylation. Specifically, selenium nanoparticles triggered an increase in the methylation of histone 3 at lysines K9 and K27, histone marks involved in both the activation and repression of gene expression, thus suggesting a fundamental role for selenium in these epigenetic processes. This direct function was confirmed using chemical inhibitors of the histone lysine methyltransferases EZH2 (H3K27) and G9a/EHMT2 (H3K9), both of which blocked the effect of selenium on histone methylation. This novel role for selenium supports a distinct function in histone methylation that occurs due to a decrease in S-adenosylhomocysteine, an endogenous inhibitor of lysine methyltransferases, the metabolic product of methyl-group transfer from S-adenosylmethionine in the one-carbon metabolism pathway. These observations provide important new insights into the action of selenium nanoparticles. It is now important to consider both the classic antioxidant and novel histone methylation effects of this key redox element in its development in cancer therapy and other applications.

Published
2023
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4. Intracellular Fate of Sub-Toxic Concentration of Functionalized Selenium Nanoparticles in Aggressive Prostate Cancer Cells

Author

Caroline Bissardon, Olivier Proux, Salvatore Andrea Gazze, Odile Filhol, Benoît Toubhans, Lucie Sauzéat, Sylvain Bouchet, Aled R. Lewis, Thierry Maffeis, Jean-Louis Hazemann, Sam Bayat, Peter Cloetens, R. Steven Conlan, Laurent Charlet, and Sylvain Bohic

Subjects
prostate cancer, selenium, nanoparticle-correlative synchrotron imaging, X-ray fluorescence, speciation, cytotoxicity, Chemistry, QD1-999
Abstract

Selenium 0 (Se0) is a powerful anti-proliferative agent in cancer research. We investigated the impact of sub-toxic concentrations of Se0 functionalized nanoparticles (SeNPs) on prostate cancer PC-3 cells and determined their intracellular localization and fate. An in-depth characterization of functionalized selenium nanoparticles composition is proposed to certify that no chemical bias relative to synthesis issues might have impacted the study. Selenium is an extremely diluted element in the biological environment and therefore requires high-performance techniques with a very low detection limit and high spatial resolution for intracellular imaging. This was explored with state-of-the-art techniques, but also with cryopreparation to preserve the chemical and structural integrity of the cells for spatially resolved and speciation techniques. Monodisperse solutions of SeNPs capped with bovine serum albumin (BSA) were shown to slow down the migration capacity of aggressive prostate cancer cells compared to polydisperse solutions of SeNPs capped with chitosan. BSA coating could prevent interactions between the reactive surface of the nanoparticles and the plasma membrane, mitigating the generation of reactive oxygen species. The intracellular localization showed interaction with mitochondria and also a localization in the lysosome-related organelle. The SeNPs-BSA localization in mitochondria constitute a possible explanation for our result showing a very significant dampening of the PC-3 cell proliferation capabilities. The purpose of the use of sublethal compound concentrations was to limit adverse effects resulting from high cell death to best evaluate some cellular changes and the fate of these SeNPs on PC-3. Our findings provide new insight to further study the various mechanisms of cytotoxicity of SeNPs.

Published
2023
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5. X-ray Phase Contrast Imaging from Synchrotron to Conventional Sources: A Review of the Existing Techniques for Biological Applications

Author

Laurene Quenot, Sylvain Bohic, and Emmanuel Brun

Subjects
X-ray imaging, phase contrast, darkfield, gratings interferometry, edge illumination, speckle based imaging, Technology, Engineering (General). Civil engineering (General), TA1-2040, Biology (General), QH301-705.5, Physics, QC1-999, Chemistry, QD1-999
Abstract

Since the seminal work of Roentgen, X-ray imaging mainly uses the same physical phenomenon: the absorption of light by matter. Thanks to third-generation synchrotrons that provide a high flux of quasi-coherent X-rays, we have seen in recent years new imaging concepts such as phase contrast or dark-field imaging that were later adapted to conventional X-ray sources. These innovative imaging techniques are particularly suitable for visualizing soft matter, such as biological tissues. After a brief introduction to the physical foundations of these two techniques, we present the different experimental set-ups that are now available to produce such contrasts: propagation, analyzer-based, grating interferometry and non-interferometric methods, such as coded aperture and modulation techniques. We present a comprehensive review of their principles; associated data processing; and finally, their requirements for their transfer outside of synchrotrons. In conclusion, gratings interferometry, coded aperture and modulation techniques seem to be the best candidates for the widespread use of phase contrast and dark-field imaging on low-cost X-ray sources.

Published
2022
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6. Radiation Dose‐Enhancement Is a Potent Radiotherapeutic Effect of Rare‐Earth Composite Nanoscintillators in Preclinical Models of Glioblastoma

Author

Anne‐Laure Bulin, Mans Broekgaarden, Frédéric Chaput, Victor Baisamy, Jan Garrevoet, Benoît Busser, Dennis Brueckner, Antonia Youssef, Jean‐Luc Ravanat, Christophe Dujardin, Vincent Motto‐Ros, Frédéric Lerouge, Sylvain Bohic, Lucie Sancey, and Hélène Elleaume

Subjects
glioblastoma, nanoscintillators, radiation dose‐enhancement, synchrotron radiation, X‐ray‐induced photodynamic therapy, Science
Abstract

Abstract To improve the prognosis of glioblastoma, innovative radiotherapy regimens are required to augment the effect of tolerable radiation doses while sparing surrounding tissues. In this context, nanoscintillators are emerging radiotherapeutics that down‐convert X‐rays into photons with energies ranging from UV to near‐infrared. During radiotherapy, these scintillating properties amplify radiation‐induced damage by UV‐C emission or photodynamic effects. Additionally, nanoscintillators that contain high‐Z elements are likely to induce another, currently unexplored effect: radiation dose‐enhancement. This phenomenon stems from a higher photoelectric absorption of orthovoltage X‐rays by high‐Z elements compared to tissues, resulting in increased production of tissue‐damaging photo‐ and Auger electrons. In this study, Geant4 simulations reveal that rare‐earth composite LaF3:Ce nanoscintillators effectively generate photo‐ and Auger‐electrons upon orthovoltage X‐rays. 3D spatially resolved X‐ray fluorescence microtomography shows that LaF3:Ce highly concentrates in microtumors and enhances radiotherapy in an X‐ray energy‐dependent manner. In an aggressive syngeneic model of orthotopic glioblastoma, intracerebral injection of LaF3:Ce is well tolerated and achieves complete tumor remission in 15% of the subjects receiving monochromatic synchrotron radiotherapy. This study provides unequivocal evidence for radiation dose‐enhancement by nanoscintillators, eliciting a prominent radiotherapeutic effect. Altogether, nanoscintillators have invaluable properties for enhancing the focal damage of radiotherapy in glioblastoma and other radioresistant cancers.

Published
2020
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7. Cellular Fractionation and Nanoscopic X-Ray Fluorescence Imaging Analyses Reveal Changes of Zinc Distribution in Leaf Cells of Iron-Deficient Plants

Author

Gianpiero Vigani, Sylvain Bohic, Franco Faoro, Bart Vekemans, Lazlo Vincze, and Roberto Terzano

Subjects
cellular fractionation, iron, nanoscopic X-ray fluorescence imaging, zinc, plant, Plant culture, SB1-1110
Abstract

Multilevel interactions among nutrients occur in the soil-plant system. Among them, Fe and Zn homeostasis in plants are of great relevance because of their importance for plant and human nutrition. However, the mechanisms underlying the interplay between Fe and Zn in plants are still poorly understood. In order to elucidate how Zn interacts with Fe homeostasis, it is crucial to assess Zn distribution either in the plant tissues or within the cells. In this study, we investigated the subcellular Zn distribution in Fe-deficient leaf cells of cucumber plants by using two different approaches: cellular fractionation coupled with inductively coupled plasma mass spectrometry (ICP/MS) and nanoscopic synchrotron X-ray fluorescence imaging. Fe-deficient leaves showed a strong accumulation of Zn as well as a strong alteration of the organelles’ ultrastructure at the cellular level. The cellular fractionation-ICP/MS approach revealed that Zn accumulates in both chloroplasts and mitochondria of Fe deficient leaves. Nano-XRF imaging revealed Zn accumulation in chloroplast and mitochondrial compartments, with a higher concentration in chloroplasts. Such results show that (i) both approaches are suitable to investigate Zn distribution at the subcellular level and (ii) cellular Fe and Zn interactions take place mainly in the organelles, especially in the chloroplasts.

Published
2018
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8. Nanoscopic X-ray fluorescence imaging and quantification of intracellular key-elements in cryofrozen Friedreich's ataxia fibroblasts.

Author

Björn De Samber, Eline Meul, Brecht Laforce, Boel De Paepe, Joél Smet, Michiel De Bruyne, Riet De Rycke, Sylvain Bohic, Peter Cloetens, Rudy Van Coster, Peter Vandenabeele, and Tom Vanden Berghe

Subjects
Medicine, Science
Abstract

Synchrotron radiation based nanoscopic X-ray fluorescence (SR nano-XRF) analysis can visualize trace level elemental distribution in a fully quantitative manner within single cells. However, in-air XRF analysis requires chemical fixation modifying the cell's chemical composition. Here, we describe first nanoscopic XRF analysis upon cryogenically frozen (-150°C) fibroblasts at the ID16A-NI 'Nano-imaging' end-station located at the European Synchrotron Radiation Facility (ESRF) in Grenoble (France). Fibroblast cells were obtained from skin biopsies from control and Friedreich's ataxia (FRDA) patients. FRDA is an autosomal recessive disorder with dysregulation of iron metabolism as a key feature. By means of the X-ray Fundamental Parameter (FP) method, including absorption correction of the ice layer deposited onto the fibroblasts, background-corrected mass fraction elemental maps of P, S, Cl, K, Ca, Fe and Zn of entire cryofrozen human fibroblasts were obtained. Despite the presence of diffracting microcrystals in the vitreous ice matrix and minor sample radiation damage effects, clusters of iron-rich hot-spots with similar mass fractions were found in the cytoplasm of both control and FRDA fibroblasts. Interestingly, no significant difference in the mean iron concentration was found in the cytoplasm of FRDA fibroblasts, but a significant decrease in zinc concentration. This finding might underscore metal dysregulation, beyond iron, in cells derived from FRDA patients. In conclusion, although currently having slightly increased limits of detection (LODs) compared to non-cryogenic mode, SR based nanoscopic XRF under cryogenic sample conditions largely obliterates the debate on chemical sample preservation and provides a unique tool for trace level elemental imaging in single cells close to their native state with a superior spatial resolution of 20 nm.

Published
2018
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9. Manganese Cytotoxicity Assay on Hippocampal Neuronal Cell Culture

Author

Alexia Daoust, Yasmina Saoudi, Jacques Brocard, Nora Collomb, Cécile Batandier, Mariano Bisbal, Murielle Salomé, Annie Andrieux, Sylvain Bohic, and Emmanuel Barbier

Subjects
Biology (General), QH301-705.5
Abstract

Compared to an in vivo experiment, neuronal cell cultures are immediately accessible to observation and manipulation. In this protocol, we describe a technique to evaluate the cytotoxicity of a metal, manganese (Mn2+), on hippocampal neuronal cell cultures. Interestingly, this protocol is easily adaptable to any type of primary culture (e.g., cortical neurons) and any type of toxic compound (e.g., chemical product).This protocol is similar to "Neuron-enriched Cultures (Method 2)" protocol (Gao, 2011).

Published
2015
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10. Iron storage within dopamine neurovesicles revealed by chemical nano-imaging.

Author

Richard Ortega, Peter Cloetens, Guillaume Devès, Asunción Carmona, and Sylvain Bohic

Subjects
Medicine, Science
Abstract

Altered homeostasis of metal ions is suspected to play a critical role in neurodegeneration. However, the lack of analytical technique with sufficient spatial resolution prevents the investigation of metals distribution in neurons. An original experimental setup was developed to perform chemical element imaging with a 90 nm spatial resolution using synchrotron-based X-ray fluorescence. This unique spatial resolution, combined to a high brightness, enables chemical element imaging in subcellular compartments. We investigated the distribution of iron in dopamine producing neurons because iron-dopamine compounds are suspected to be formed but have yet never been observed in cells. The study shows that iron accumulates into dopamine neurovesicles. In addition, the inhibition of dopamine synthesis results in a decreased vesicular storage of iron. These results indicate a new physiological role for dopamine in iron buffering within normal dopamine producing cells. This system could be at fault in Parkinson's disease which is characterized by an increased level of iron in the substantia nigra pars compacta and an impaired storage of dopamine due to the disruption of vesicular trafficking. The re-distribution of highly reactive dopamine-iron complexes outside neurovesicles would result in an enhanced death of dopaminergic neurons.

Published
2007
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11. Why are amyloid-β plaques detected by X-ray phase-contrast imaging? Role of metals revealed through combined synchrotron infrared and X-ray fluorescence microscopies

Author

Matthieu Chourrout, Christophe Sandt, Timm Weitkamp, Tanja Dučić, David Meyronet, Thierry Baron, Jan Klohs, Nicolas Rama, Hervé Boutin, Shifali Singh, Cécile Olivier, Marlène Wiart, Emmanuel Brun, Sylvain Bohic, and Fabien Chauveau

Abstract

Amyloid-β (Aβ) plaques from Alzheimer’s Disease (AD) can be visualizedex vivoin label-free brain samples using synchrotron X-ray phase-contrast tomography (XPCT). However, for XPCT to be useful as a screening method for amyloid pathology, it is essential to understand which factors drive the detection of Aβ plaques. The current study was designed to test the hypothesis that Aβ-related contrast in XPCT could be caused by the Aβ fibrils and/or by metals trapped in the plaques. This study probed the fibrillar and elemental compositions of Aβ plaques in brain samples from different types of AD patients and AD models to establish a relationship between XPCT contrast and Aβ plaque characteristics. XPCT, micro-Fourier-Transform Infrared spectroscopy and micro-X-Ray Fluorescence spectroscopy were conducted on human samples (genetic and sporadic cases) and on four transgenic rodent strains (mouse: APPPS1, ArcAβ, J20; rat: TgF344). Aβ plaques from the genetic AD patient were visible using XPCT, and had higher β–sheet content and higher metal levels than the sporadic AD patient, which remained undetected by XPCT. Aβ plaques in J20 mice and TgF344 rats appeared hyperintense on XPCT images, while they were hypointense with an hyperintense core in the case of APPPS1 and ArcAβ mice. In all four transgenic strains, β-sheet content was similar, while metal levels were highly variable: J20 (zinc and iron) and TgF344 (copper) strains showed greater metal accumulation than APPPS1 and ArcAβ mice. Hence, a positive contrast formation of Aβ plaques in XPCT images appeared driven by biometal entrapment.Graphical AbstractHighlightsAmyloid-β plaques in the different forms of Alzheimer’s Disease have various contrasts in X-ray phase-contrast tomographyIn transgenic rodents, a core-restricted, positive contrast is driven by the level of metal entrapment within plaquesIn humans, greater and more diffuse metal accumulation lead to a positive contrast in a genetic case of AD

Published
2022
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13. Biological Samples Preparation for Speciation at Cryogenic Temperature using High-Resolution X-Ray Absorption Spectroscopy

Author

Sylvain Bohic, Olivier Proux, Eric Lahera, Mauro Rovezzi, Emmanuel Lesuisse, Marie-Pierre Isaure, and Caroline Bissardon

Subjects
Selenium, X-Ray Absorption Spectroscopy, General Immunology and Microbiology, Metals, General Chemical Engineering, General Neuroscience, Temperature, General Biochemistry, Genetics and Molecular Biology
Abstract

The study of elements with X-ray absorption spectroscopy (XAS) is of particular interest when studying the role of metals in biological systems. Sample preparation is a key and often complex procedure, particularly for biological samples. Although X-ray speciation techniques are widely used, no detailed protocol has been yet disseminated for users of the technique. Further, chemical state modification is of concern, and cryo-based techniques are recommended to analyze the biological samples in their near-native hydrated state to provide the maximum preservation of chemical integrity of the cells or tissues. Here, we propose a cellular preparation protocol based on cryo-preserved samples. It is demonstrated in a high energy resolution fluorescence detected X-ray absorption spectroscopy study of selenium in cancer cells and a study of iron in phytoplankton. This protocol can be used with other biological samples and other X-ray techniques that can be damaged by irradiation.

Published
2022
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14. The Zinc Ionophore Clioquinol Reduces Parkinson's Disease Patient-Derived Brain Extracts-Induced Neurodegeneration

Author

Margaux Teil, Evelyne Doudnikoff, Marie-Laure Thiolat, Sylvain Bohic, Erwan Bezard, Benjamin Dehay, Dehay, Benjamin, Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Synchrotron Radiation for Biomedicine = Rayonnement SynchroTROn pour la Recherche BiomédicalE (STROBE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), and Centre Broca Nouvelle Aquitaine [Neurocampus Bordeaux] (CBNA)

Subjects
α-Synuclein, Ionophores, Tissue Extracts, Dopamine, Dopaminergic Neurons, Neuroscience (miscellaneous), Brain, Clioquinol, Parkinson Disease, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Substantia Nigra, Cellular and Molecular Neuroscience, Mice, Zinc, Neurology, nervous system, Parkinson’s disease, [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], alpha-Synuclein, Animals, Humans
Abstract

Background: Parkinson’s Disease (PD) is characterized by the presence of intracellular α-synuclein-rich protein aggregates, named Lewy Bodies (LB), and by the progressive loss of dopaminergic neurons in the substantia nigra. Several heavy metals, including zinc (Zn), have been suggested to play a role in PD progression, although the exact role of Zn in neurodegeneration remains to be fully elucidated.Methods: To address this gap, we investigated the effects of Zn modulation on the progression of degeneration in mice injected with PD patient-derived LB-extracts carrying toxic a-synuclein aggregates. Zn modulation was achieved using either a clioquinol-enriched diet, a Zn ionophore that redistributes cellular Zn, or a Zn-enriched diet that increases Zn levels. Results: Clioquinol treatment significantly prevented dopaminergic neurodegeneration and reduced α-synuclein-associated pathology in LB-injected mice while no differences were observed with Zn supplementation. Biochemical analyses further demonstrate that the expression levels of vesicle-specific Zn transporter ZnT3 in the striatum of LB-injected mice treated with clioquinol were decreased, suggesting an intracellular redistribution of Zn. Additionally, we found that clioquinol modulates the autophagy-lysosomal pathway by enhancing lysosomal redistribution within the neuronal compartments. Conclusions: Collectively, we found that in vivo pharmacological chelation of Zn, by dampening Zn-mediated cytotoxicity, can result in an overall attenuation of PD-linked lysosomal alterations and dopaminergic neurodegeneration. The results support zinc chelation as a disease-modifying strategy for the treatment of PD.

Published
2022
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15. X-ray Phase Contrast Imaging from Synchrotron to Conventional Sources: A Review of the Existing Techniques for Biological Applications

Author

Emmanuel Brun, Laurene QUENOT, and Sylvain BOHIC

Subjects
Fluid Flow and Transfer Processes, Process Chemistry and Technology, General Engineering, General Materials Science, Instrumentation, Computer Science Applications
Abstract

Since the seminal work of Roentgen, X-ray imaging mainly uses the same physical phenomenon: the absorption of light by matter. Thanks to third-generation synchrotrons that provide a high flux of quasi-coherent X-rays, we have seen in recent years new imaging concepts such as phase contrast or dark-field imaging that were later adapted to conventional X-ray sources. These innovative imaging techniques are particularly suitable for visualizing soft matter, such as biological tissues. After a brief introduction to the physical foundations of these two techniques, we present the different experimental set-ups that are now available to produce such contrasts: propagation, analyzer-based, grating interferometry and non-interferometric methods, such as coded aperture and modulation techniques. We present a comprehensive review of their principles; associated data processing; and finally, their requirements for their transfer outside of synchrotrons. In conclusion, gratings interferometry, coded aperture and modulation techniques seem to be the best candidates for the widespread use of phase contrast and dark-field imaging on low-cost X-ray sources.

Published
2022
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16. Three-Dimensional Correlative Imaging of a Malaria-Infected Cell with a Hard X-ray Nanoprobe

Author

Alexandra Pacureanu, W. De Nolf, Christophe Biot, Peter Cloetens, Florin Fus, Yang Yang, J. C. da Silva, Sylvain Bohic, Université de Lille, CNRS, Université de Lille, Sciences et Technologies, Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576, Department of Mechanical Engineering [Hong Kong], The Hong Kong Polytechnic University [Hong Kong] (POLYU), and European Synchrotron Radiation Facility (ESRF)

Subjects
Correlative, X-ray nanoprobe, Erythrocytes, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Plasmodium falciparum, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], 010402 general chemistry, 01 natural sciences, Analytical Chemistry, law.invention, Nuclear magnetic resonance, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, law, Infected cell, Humans, Tomographic reconstruction, Pixel, Chemistry, 010401 analytical chemistry, X-Ray Microtomography, Synchrotron, 3. Good health, 0104 chemical sciences, Correlative imaging, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, Mass fraction
Abstract

International audience; Benefiting from the recent advances of synchrotron X-ray nanoprobes, we demonstrate three-dimensional (3D) correlative nano-imaging on malaria-infected human red blood cells. By combining X-ray fluorescence to-mography and phase contrast nanotomography on the same cell with sub-100 nm pixel size, we establish a routine workflow from the data acquisition, data processing to tomographic reconstruction. We quantitatively compare the elemental volumes obtained with different reconstruction methods, the total variation minimization giving the most satisfactory results. We reveal elemental correlations in different cell compartments more reliably on reconstructions as opposed to 2D projections. Finally, we determine for the first time the 3D mass fraction maps of multiple elements at sub-cellular level. The estimated total number of Fe atoms and the total mass of the red blood cell show very good agreement with previously reported values.

Published
2019
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17. Zinc Uptake and Storage During the Formation of the Cerebral Cortex in Mice

Author

Sophie Lemoine, Alexandre Bouron, Jessy Hasna, Corinne Blugeon, Sylvain Bohic, Biologie des Métaux (BioMet), Laboratoire de Chimie et Biologie des Métaux (LCBM - UMR 5249), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), European Synchrotron Radiation Facility (ESRF), Institut de biologie de l'ENS Paris (IBENS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de biologie de l'ENS Paris (UMR 8197/1024) (IBENS), Département de Biologie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), GenomiqueENS (Genomique ENS), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Département de Biologie - ENS Paris, and ANR-16-CE29-0024,ImaZinc,Homéostasie du zinc lors de la corticogénese(2016)

Subjects
0301 basic medicine, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Neuroscience (miscellaneous), Embryonic Development, Transcriptome, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Cortex (anatomy), medicine, Animals, Cerebral Cortex, Neurons, Neocortex, Chemistry, Embryogenesis, Membrane Transport Proteins, Reproducibility of Results, Embryonic stem cell, Cell biology, Mice, Inbred C57BL, Zinc, Corticogenesis, 030104 developmental biology, medicine.anatomical_structure, Neurology, Cerebral cortex, 030217 neurology & neurosurgery, Homeostasis, Transcription Factors
Abstract

International audience; The cerebral cortex (or neocortex) is a brain structure formed during embryogenesis. The present study seeks to provide a detailed characterization of the Zn homeostatic mechanisms during cerebral cortex formation and development. To reach that goal, we have combined high-throughput RNA-sequencing analysis of the whole murine genome, X-ray fluorescence nanoimaging (XRF), inductively coupled plasma-atomic emission spectrometry (ICP-AES), and live-cell imaging of dissociated cortical neurons loaded with the Zn fluorescent probe FluoZin-3. The transcriptomic analysis was conducted from mRNAs isolated from cortices collected at embryonic (E) days 11 (E11), E13, and E17 and on postnatal day 1 (PN1) pups. This permitted to characterize the temporal pattern of expression of the main genes participating in the cellular transport, storage, and release of Zn during corticogenesis. It appears that cells of the immature cortex express a wide diversity of actors involved in Zn homeostasis with Zip7, SOD1, and metallothioneins being the most abundant transcripts throughout corticogenesis. The quantification of total Zn with XRF and ICP-AES reveals a reduction of Zn levels. Moreover, this is accompanied by a diminution of the size of the internal pools of mobilizable Zn. This study illustrates the tight temporal and spatial regulation of Zn homeostasis during cerebral brain development.

Published
2019
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19. Selenium nanoparticles trigger alterations in ovarian cancer cell biomechanics

Author

Lewis Francis, Laurent Charlet, R. Steven Conlan, Alexandra T. Gourlan, Benoit Toubhans, Deyarina Gonzalez, Sylvain Bohic, Salvatore A. Gazze, Caroline Bissardon, Institut des Sciences de la Terre (ISTerre), Institut national des sciences de l'Univers (INSU - CNRS)-Institut de recherche pour le développement [IRD] : UR219-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Gustave Eiffel-Université Grenoble Alpes (UGA), Swansea University Medical School [Swansea, Royaume-Uni], Swansea University, Synchrotron Radiation for Biomedicine = Rayonnement SynchroTROn pour la Recherche BiomédicalE (STROBE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), CCSD, Accord Elsevier, and European Synchrotron Radiation Facility (ESRF)

Subjects
Cell type, Programmed cell death, endocrine system diseases, [SDV]Life Sciences [q-bio], Biomedical Engineering, Metal Nanoparticles, Pharmaceutical Science, Medicine (miscellaneous), chemistry.chemical_element, Antineoplastic Agents, Apoptosis, Bioengineering, 02 engineering and technology, Carcinoma, Ovarian Epithelial, Metastasis, Cell membrane, 03 medical and health sciences, Selenium, Cell Line, Tumor, medicine, Humans, General Materials Science, Cytotoxicity, Cell Proliferation, 030304 developmental biology, Ovarian Neoplasms, 0303 health sciences, Chemistry, Cell growth, 021001 nanoscience & nanotechnology, medicine.disease, female genital diseases and pregnancy complications, Nanomechanics, Biomechanical Phenomena, 3. Good health, Ovarian Cancer, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, Cancer research, Molecular Medicine, Nanoparticles, Female, 0210 nano-technology, Ovarian cancer
Abstract

International audience; High dose selenium acts as a cytotoxic agent, with potential applications in cancer treatment. However, clinical trials have failed to show any chemotherapeutic value of selenium at safe and tolerated doses (

Published
2020
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20. Radiation Dose-Enhancement Is a Potent Radiotherapeutic Effect of Rare-Earth Composite Nanoscintillators in Preclinical Models of Glioblastoma

Author

Dennis Brueckner, Sylvain Bohic, Benoit Busser, Lucie Sancey, Frédéric Chaput, Vincent Motto-Ros, Frédéric Lerouge, Jan Garrevoet, Jean-Luc Ravanat, Mans Broekgaarden, Hélène Elleaume, Christophe Dujardin, Victor Baisamy, Antonia Youssef, Anne-Laure Bulin, Synchrotron Radiation for Biomedicine = Rayonnement SynchroTROn pour la Recherche BiomédicalE (STROBE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Laboratoire de Chimie - UMR5182 (LC), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-École normale supérieure - Lyon (ENS Lyon)-Institut de Chimie du CNRS (INC), Deutsches Elektronen-Synchrotron [Zeuthen] (DESY), Helmholtz-Gemeinschaft = Helmholtz Association, Cancer Targets & Experimental Therapeutics, Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Chimie Interface Biologie pour l’Environnement, la Santé et la Toxicologie (CIBEST ), SYstèmes Moléculaires et nanoMatériaux pour l’Energie et la Santé (SYMMES), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), Département Interfaces pour l'énergie, la Santé et l'Environnement (DIESE), Luminescence (LUMINESCENCE), Institut Lumière Matière [Villeurbanne] (ILM), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Spectrométrie des biomolécules et agrégats (SPECTROBIO), ANR-11-LABX-0063,PRIMES,Physique, Radiobiologie, Imagerie Médicale et Simulation(2011), ANR-11-INBS-0006,FLI,France Life Imaging(2011), Lerouge, Frédéric, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), European Synchroton Radiation Facility [Grenoble] (ESRF), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Rayet, Béatrice, Physique, Radiobiologie, Imagerie Médicale et Simulation - - PRIMES2011 - ANR-11-LABX-0063 - LABX - VALID, Infrastructures - France Life Imaging - - FLI2011 - ANR-11-INBS-0006 - INBS - VALID, and École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL)

Subjects
Materials science, General Chemical Engineering, medicine.medical_treatment, Rare earth, GLIOBLASTOMA, General Physics and Astronomy, Medicine (miscellaneous), Context (language use), [SDV.CAN]Life Sciences [q-bio]/Cancer, 02 engineering and technology, 010402 general chemistry, 01 natural sciences, Biochemistry, Genetics and Molecular Biology (miscellaneous), radiation dose‐enhancement, RADIATION THERAPY, [SDV.CAN] Life Sciences [q-bio]/Cancer, Radioresistance, medicine, General Materials Science, lcsh:Science, Full Paper, synchrotron radiation, Spatially resolved, Radiation dose, X‐ray‐induced photodynamic therapy, General Engineering, glioblastoma, Full Papers, RADIATION DOSE ENHANCEMENT, 021001 nanoscience & nanotechnology, medicine.disease, 0104 chemical sciences, 3. Good health, NANOSCINTILLATORS, Radiation therapy, nanoscintillators, Photoelectric absorption, Cancer research, lcsh:Q, 0210 nano-technology, Glioblastoma, ddc:624
Abstract

Advanced science xx, 2001675 (1-18) (2020). doi:10.1002/advs.202001675, To improve the prognosis of glioblastoma, innovative radiotherapy regimens are required to augment the effect of tolerable radiation doses while sparing surrounding tissues. In this context, nanoscintillators are emerging radiotherapeutics that down‐convert X‐rays into photons with energies ranging from UV to near‐infrared. During radiotherapy, these scintillating properties amplify radiation‐induced damage by UV‐C emission or photodynamic effects. Additionally, nanoscintillators that contain high‐Z elements are likely to induce another, currently unexplored effect: radiation dose‐enhancement. This phenomenon stems from a higher photoelectric absorption of orthovoltage X‐rays by high‐Z elements compared to tissues, resulting in increased production of tissue‐damaging photo‐ and Auger electrons. In this study, Geant4 simulations reveal that rare‐earth composite LaF$_3$:Ce nanoscintillators effectively generate photo‐ and Auger‐electrons upon orthovoltage X‐rays. 3D spatially resolved X‐ray fluorescence microtomography shows that LaF$_3$:Ce highly concentrates in microtumors and enhances radiotherapy in an X‐ray energy‐dependent manner. In an aggressive syngeneic model of orthotopic glioblastoma, intracerebral injection of LaF$_3$:Ce is well tolerated and achieves complete tumor remission in 15% of the subjects receiving monochromatic synchrotron radiotherapy. This study provides unequivocal evidence for radiation dose‐enhancement by nanoscintillators, eliciting a prominent radiotherapeutic effect. Altogether, nanoscintillators have invaluable properties for enhancing the focal damage of radiotherapy in glioblastoma and other radioresistant cancers., Published by Wiley-VCH, Weinheim

Published
2020
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21. Cryo-nanoimaging of Single Human Macrophage Cells: 3D Structural and Chemical Quantification

Author

Alessandra Procopio, Sylvain Bohic, Francesca Berlutti, Chiara Gramaccioni, Piera Valenti, Peter Cloetens, Nicola Viganò, Luigi Rosa, Yang Yang, and Alexandra Pacureanu

Subjects
Surface Properties, X-ray fluorescence, x-rays, tomography, 010402 general chemistry, 01 natural sciences, Analytical Chemistry, immunology, Optical imaging, Single-cell analysis, Microscopy, elements, fluorescence, Humans, Particle Size, Chemistry, Macrophages, 010401 analytical chemistry, Cryoelectron Microscopy, Optical Imaging, Fluorescence, Macrophage (ecology), 0104 chemical sciences, Biophysics, Nanoparticles, Single-Cell Analysis
Abstract

X-ray microscopy is increasingly used in biology, but in most cases only in a qualitative way. We present here a 3D correlative cryo X-ray microscopy approach suited for the quantification of molar concentrations and structure in native samples at nanometer scale. The multimodal approach combines X-ray fluorescence and X-ray holographic nanotomography on "thick" frozen-hydrated cells. The quantitativeness of the X-ray fluorescence reconstruction is improved by estimating the self-attenuation from the 3D holography reconstruction. Applied to complex macrophage cells, we extract the quantification of major and minor elements heavier than phosphorus, as well as the density, in the different organelles. The intracellular landscape shows remarkable elemental differences. This novel analytical microscopy approach will be of particular interest to investigate complex biological and chemical systems in their native environment.

Published
2020

22. Subcellular Chemical Imaging: New Avenues in Cell Biology

Author

Pietro Benettoni, Benoit Gallet, Giulia Veronesi, Sylvain Bohic, Rémi Tucoulou, Johan Decelle, Matthias Schmidt, Peta L. Clode, Niculina Musat, Hryhoriy Stryhanyuk, Melissa K. Passarelli, Light Photosynthesis & Metabolism (Photosynthesis), Physiologie cellulaire et végétale (LPCV), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Grenoble Alpes (UGA), Groupe modélisation et chimie théorique (MCT ), Laboratoire de Chimie et Biologie des Métaux (LCBM - UMR 5249), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), European Synchrotron Radiation Facility (ESRF), Groupe Microscopie Electronique et Méthodes (IBS-MEM), Institut de biologie structurale (IBS - UMR 5075), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Helmholtz Centre for Environmental Research, Department of Isotope Biogeochemistry (UFZ), Laboratory for Biological Geochemistry, École Polytechnique Fédérale de Lausanne (EPFL), Synchrotron Radiation for Biomedicine = Rayonnement SynchroTROn pour la Recherche BiomédicalE (STROBE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Centre for Microscopy, Characterisation and Analysis (CMCA), The University of Western Australia (UWA), UWA School of Biological Sciences, Défi X-Life grant from CNRS, Landmark ESFRI project, ANR-10-LABX-0049,GRAL,Grenoble Alliance for Integrated Structural Cell Biology(2010), ANR-17-EURE-0003,CBH-EUR-GS,CBH-EUR-GS(2017), ANR-10-INBS-0002,EMBRC-France,CENTRE NATIONAL DE RESSOURCES BIOLOGIQUES MARINES(2010), Université Grenoble Alpes (UGA)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Centre National de la Recherche Scientifique (CNRS), Groupe modélisation et chimie théorique (MCT), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS), Synchrotron Radiation for Biomedicine [Grenoble] (STROBE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), GON, Nathalie, Grenoble Alliance for Integrated Structural Cell Biology - - GRAL2010 - ANR-10-LABX-0049 - LABX - VALID, CBH-EUR-GS - - CBH-EUR-GS2017 - ANR-17-EURE-0003 - EURE - VALID, Infrastructures - CENTRE NATIONAL DE RESSOURCES BIOLOGIQUES MARINES - - EMBRC-France2010 - ANR-10-INBS-0002 - INBS - VALID, and Ecole Polytechnique Fédérale de Lausanne (EPFL)

Subjects
Chemical imaging, Elemental imaging, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Cells, elemental imaging, x-ray-fluorescence, Correlative microscopy, X-ray fluorescence, neurons, Computational biology, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, ion mass-spectrometry, Multimodal Imaging, localization, nanosims, 03 medical and health sciences, 0302 clinical medicine, Imaging, Three-Dimensional, Animals, Humans, correlative microscopy, chemical imaging, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, 030304 developmental biology, lateral resolution, 0303 health sciences, electron microscopy, Cell Biology, elements, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, speciation, reveals, SIMS, electron-microscopy, 030217 neurology & neurosurgery, Subcellular Fractions
Abstract

International audience; To better understand the physiology and acclimation capability of the cell, one of the great challenges of the future is to access the interior of a cell and unveil its chemical landscape (composition and distribution of elements and molecules). Chemical imaging has greatly improved in sensitivity and spatial resolution to visualize and quantify nutrients, metabolites, toxic elements, and drugs in single cells at the subcellular level. This review aims to present the current potential of these emerging imaging technologies and to guide biologists towards a strategy for interrogating biological processes at the nanoscale. We also describe various solutions to combine multiple imaging techniques in a correlative way and provide perspectives and future directions for integrative subcellular imaging across different disciplines

Published
2020
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23. A liver-targeting Cu(l) chelator relocates Cu in hepatocytes and promotes Cu excretion in a murine model of Wilson's disease

Author

Khémary Um, Elisabeth Mintz, Anaïs Pujol, Vincent Balter, Virginie Brun, Sylvain Bohic, Marie Monestier, Peggy Charbonnier, Doris Cassio, Amélie Harel, Martine Cuillel, Isabelle Pignot-Paintrand, Christelle Gateau, Aline Lamboux, Pascale Delangle, Biologie des Métaux (BioMet ), Laboratoire de Chimie et Biologie des Métaux (LCBM - UMR 5249), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), Chimie Interface Biologie pour l’Environnement, la Santé et la Toxicologie (CIBEST ), SYstèmes Moléculaires et nanoMatériaux pour l’Energie et la Santé (SYMMES), Département Interfaces pour l'énergie, la Santé et l'Environnement (DIESE), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Laboratoire de Géologie de Lyon - Terre, Planètes, Environnement (LGL-TPE), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut national des sciences de l'Univers (INSU - CNRS)-Université Jean Monnet - Saint-Étienne (UJM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire des matériaux et du génie physique (LMGP ), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA)-Université Grenoble Alpes (UGA), Interactions Cellulaires et Physiopathologie Hépatique [Orsay], Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Synchrotron Radiation for Biomedicine = Rayonnement SynchroTROn pour la Recherche BiomédicalE (STROBE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Etude de la dynamique des protéomes (EDyP ), Laboratoire de Biologie à Grande Échelle (BGE - UMR S1038), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), ANR-17-EURE-0003,CBH-EUR-GS,CBH-EUR-GS(2017), Laboratoire de Géologie de Lyon - Terre, Planètes, Environnement [Lyon] (LGL-TPE), Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-École normale supérieure - Lyon (ENS Lyon), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])

Subjects
0301 basic medicine, Biophysics, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, 010402 general chemistry, Bone canaliculus, 01 natural sciences, Biochemistry, Biomaterials, Excretion, 03 medical and health sciences, Mice, Hepatolenticular Degeneration, medicine, Animals, Chelation, [CHIM.COOR]Chemical Sciences/Coordination chemistry, Microscopy, Confocal, Chemistry, Metals and Alloys, Ceruloplasmin, Spectrometry, X-Ray Emission, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Copper Chelation, medicine.disease, 3. Good health, 0104 chemical sciences, Cell biology, Wilson's disease, Disease Models, Animal, 030104 developmental biology, Mechanism of action, Chemistry (miscellaneous), Hepatic stellate cell, Hepatocytes, medicine.symptom, Intracellular, Copper
Abstract

Copper chelation is the most commonly used therapeutic strategy nowadays to treat Wilson’s disease, a genetic disorder primarily inducing a pathological accumulation of Cu in the liver. The mechanism of action of Chel2, a liver-targeting Cu(i) chelator known to promote intracellular Cu chelation, was studied in hepatic cells that reconstitute polarized epithelia with functional bile canaliculi, reminiscent of the excretion pathway in the liver. The interplay between Chel2 and Cu localization in these cells was demonstrated through confocal microscopy using a fluorescent derivative and nano X-ray fluorescence. The Cu(i) bound chelator was found in vesicles potentially excreted in the canaliculi. Moreover, injection of Chel2 either intravenously or subcutaneously to a murine model of Wilson’s disease increased excretion of Cu in the faeces, confirming in vivo biliary excretion. Therefore, Chel2 turns out to be a possible means to collect and excrete hepatic Cu in the faeces, hence restoring the physiological pathway.

Published
2020
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24. Nanoscopic X-ray imaging and quantification of the iron cellular architecture within single fibroblasts of Friedreich's ataxia patients

Author

Martin Seyrich, Peter Cloetens, Rudy Van Coster, Peter Vandenabeele, Julio Cesar da Silva, Joél Smet, Björn De Samber, Eline Meul, Sylvain Bohic, Stephen Bauters, Tom Vanden Berghe, Laszlo Vincze, Boel De Paepe, Universiteit Gent = Ghent University [Belgium] (UGENT), Universiteit Antwerpen [Antwerpen], Deutsches Elektronen-Synchrotron [Hamburg] (DESY), Ghent University Hospital, Matériaux, Rayonnements, Structure (MRS), Institut Néel (NEEL), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA), European Synchrotron Radiation Facility (ESRF), Institut National de la Santé et de la Recherche Médicale (INSERM), DA SILVA, Julio, Universiteit Gent = Ghent University (UGENT), Universiteit Antwerpen = University of Antwerpen [Antwerpen], and Matériaux, Rayonnements, Structure (NEEL - MRS)

Subjects
Cytoplasm, Tissue Fixation, [SPI.OPTI] Engineering Sciences [physics]/Optics / Photonic, [SDV]Life Sciences [q-bio], Cell, Holography, Mitochondrion, 0302 clinical medicine, iron, ddc:550, Instrumentation, 0303 health sciences, Radiation, Chemistry, Physics, imaging, 3. Good health, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, medicine.symptom, Single-Cell Analysis, Nuclear and High Energy Physics, Ataxia, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, 03 medical and health sciences, Organelle, medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Fibroblast, Nanoscopic scale, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, 030304 developmental biology, Organelles, Endoplasmic reticulum, Spectrometry, X-Ray Emission, Friedreich's ataxia, nano-XRF, Fibroblasts, Carbon, quantification, Nanostructures, Cytosol, Freeze Drying, Friedreich Ataxia, Biophysics, [SPI.OPTI]Engineering Sciences [physics]/Optics / Photonic, 030217 neurology & neurosurgery, Synchrotrons
Abstract

International audience; Friedreich's ataxia (FRDA) is a neurodegenerative disease characterized by an increase in intracytoplasmic iron concentration. Here the nanoscale iron distribution within single fibroblasts from FRDA patients was investigated using synchrotron-radiation-based nanoscopic X-ray fluorescence and X-ray in-line holography at the ID16A nano-imaging beamline of the ESRF. This unique probe was deployed to uncover the iron cellular two-dimensional architecture of freeze-dried FRDA fibroblasts. An unsurpassed absolute detection capability of 180 iron atoms within a 30 nm  50 nm nanoscopic X-ray beam footprint was obtained using state-of-the-art X-ray focusing optics and a large-solid-angle detection system. Various micrometre-sized iron-rich organelles could be revealed for the first time, tentatively identified as endoplasmic reticulum, mitochondria and lysosomes. Also a multitude of nanoscopic iron hot-spots were observed in the cytosol, interpreted as chaperoned iron within the fibroblast's labile iron pool. These observations enable new hypotheses on the storage and trafficking of iron in the cell and ultimately to a better understanding of iron-storage diseases such as Friedreich's ataxia.

Published
2020
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25. Nanopositioning for the ESRF ID16A Nano-Imaging Beamline

Author

Sylvain Bohic, Alexandra Pacureanu, Cyril Guilloud, Yang Yang, Manuel Gil Pérez, J. C. da Silva, J. Meyer, O. Hignette, Murielle Salomé, R. Baker, F. Villar, P. van der Linden, Peter Cloetens, and L. Andre

Subjects
0301 basic medicine, 030103 biophysics, Nuclear and High Energy Physics, Mesoscopic physics, Materials science, Scale (ratio), Nanotechnology, 02 engineering and technology, 021001 nanoscience & nanotechnology, Atomic and Molecular Physics, and Optics, 03 medical and health sciences, Beamline, Characterization methods, Nano, Nanometre, 0210 nano-technology
Abstract

New scientific frontiers in biomedicine, materials science, and nanotechnology make increasing use of characterization methods at the mesoscopic and nanometer scale. These studies of heterogeneous ...

Published
2018
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26. Cell Culture on Silicon Nitride Membranes and Cryopreparation for Synchrotron X-ray Fluorescence Nano-analysis

Author

Caroline, Bissardon, Solveig, Reymond, Murielle, Salomé, Lionel, André, Sam, Bayat, Peter, Cloetens, and Sylvain, Bohic

Subjects
General Immunology and Microbiology, General Chemical Engineering, General Neuroscience, Silicon Compounds, Cell Culture Techniques, Humans, Fluorescence, Synchrotrons, General Biochemistry, Genetics and Molecular Biology
Abstract

Very little is known about the distribution of metal ions at the subcellular level. However, those chemical elements have essential regulatory functions and their disturbed homeostasis is involved in various diseases. State-of-the-art synchrotron X-ray fluorescence nanoprobes provide the required sensitivity and spatial resolution to elucidate the two-dimensional (2D) and three-dimensional (3D) distribution and concentration of metals inside entire cells at the organelle level. This opens new exciting scientific fields of investigation on the role of metals in the physiopathology of the cell. The cellular preparation is a key and often complex procedure, particularly for basic analysis. Although X-ray fluorescence techniques are now widespread and various preparation methods have been used, very few studies have investigated the preservation of the elemental content of cells at best, and no stepwise detailed protocol for the cryopreparation of adherent cells for X-ray fluorescence nanoprobes has been released so far. This is a description of a protocol that provides the stepwise cellular preparation for fast cryofixation to enable synchrotron X-ray fluorescence nano-analysis of cells in a frozen hydrated state when a cryogenic environment and transfer is available. In case nano-analysis has to be performed at room temperature, an additional procedure for freeze-drying the cryofixed adherent cellular preparation is provided. The proposed protocols have been successfully used in previous works, most recently in studying the 2D and 3D intracellular distribution of an organometallic compound in breast cancer cells.

Published
2019
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27. Implicit tracking approach for X-ray phase-contrast imaging with a random mask and a conventional system

Author

Emmanuel Brun, Hélène Rougé-Labriet, Sylvain Bohic, Laurène Quénot, Sebastien Berujon, Synchrotron Radiation for Biomedicine = Rayonnement SynchroTROn pour la Recherche BiomédicalE (STROBE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Laboratoire de recherche en imagerie et orthopédie [Montréal] (LIO), Ecole de Technologie Supérieure [Montréal] (ETS)-Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), Instituto COPPEAD de Administração, Universidade Federal do Estado do Rio de Janeiro (UNIRIO), and Rayet, Béatrice

Subjects
[SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Computer science, business.industry, Detector, Phase-contrast imaging, Image processing, Atomic and Molecular Physics, and Optics, Electronic, Optical and Magnetic Materials, Speckle pattern, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, Optics, X-Ray Phase-Contrast Imaging, Optical transfer function, business, Phase retrieval, Coherence (physics)
Abstract

International audience; X-ray phase contrast imaging (PCI) has shown great potential for clinical investigation of soft tissues. However, most of the existing X-ray PCI modalities require either a partially coherent source such as a synchrotron or complex setups that are barely compatible with low-dose and patient tomography. This work demonstrates the possibility to efficiently achieve PCI on a low coherence system with a conventional X-ray tube and a detector compatible with a clinical routine. This was accomplished by adapting the speckle-based imaging setup and the numerical phase retrieval processing methods to the low coherence and the low resolution of the experiment.

Published
2021
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28. Coherent X-ray imaging on ID16A: status and plans

Author

Dmitry Karpov, Federico Monaco, Sylvain Bohic, Murielle Salome, Vincent Favre-Nicolin, Alexandra Teodora Joita Pacureanu, and Peter Cloetens

Subjects
Inorganic Chemistry, Structural Biology, General Materials Science, Physical and Theoretical Chemistry, Condensed Matter Physics, Biochemistry
Published
2021
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29. Intracellular localization of an osmocenyl-tamoxifen derivative in breast cancer cells revealed by synchrotron radiation X-ray fluorescence nanoimaging

Author

Michèle Salmain, Sylvain Bohic, Alexandra Pacureanu, Julio Cesar da Silva, Hui Zhi Shirley Lee, Anne Vessières, Florin Fus, Marie Carrière, Peter Cloetens, Alexandre Bouron, Yang Yang, Siden Top, Gerard Jaouen, Laboratoire Rayonnement Synchrotron et Recherche Médicale (EA 7442), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), European Synchrotron Radiation Facility (ESRF), Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL), Institut Parisien de Chimie Moléculaire (IPCM), Chimie Moléculaire de Paris Centre (FR 2769), Institut de Chimie du CNRS (INC)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Chimie Interface Biologie pour l’Environnement, la Santé et la Toxicologie (CIBEST ), SYstèmes Moléculaires et nanoMatériaux pour l’Energie et la Santé (SYMMES), Institut de Chimie du CNRS (INC)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Biologie des Métaux (BioMet), Laboratoire de Chimie et Biologie des Métaux (LCBM - UMR 5249), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)

Subjects
X-ray fluorescence, Triple Negative Breast Neoplasms, Ligands, 01 natural sciences, law.invention, law, Coordination Complexes, Chemistry, Bioorganometallic chemistry, osmium, Hydrogen-Ion Concentration, Fluorescence, Synchrotron, 3. Good health, Molecular Imaging, Membrane, Female, medicine.symptom, [CHIM.RADIO]Chemical Sciences/Radiochemistry, Intracellular, Iron, Static Electricity, Antineoplastic Agents, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, 010402 general chemistry, Catalysis, Ruthenium, Cell Line, Tumor, synchrotron, medicine, Organometallic Compounds, Molecule, Humans, Endomembrane system, [CHIM.COOR]Chemical Sciences/Coordination chemistry, metallodrug, 010405 organic chemistry, bioorganometallic chemistry, X-Rays, Cell Membrane, General Chemistry, 0104 chemical sciences, Nanostructures, Radiography, Tamoxifen, elemental tomography, Mechanism of action, Molecular Probes, Biophysics, Synchrotrons, breast cancer cells
Abstract

International audience; We have recently developed a series of tamoxifen-like metallocifens of the group-8 metals (Fe, Ru and Os) with strong antiproliferative activity on the triple negative breast cancer cells (MDA-MB-231). This property, not observed for the organic analog 4-hydroxytamoxifen, has been associated with the unique redox behavior of metallocenic moieties, readily affording reactive quinone methides in cancer cells. To shed light on the mechanism of action of these molecules, synchrotron radiation X-ray fluorescence (SR-XRF) nanoimaging studies were performed on cells exposed to osmocenyltamoxifen (Oc-OH-Tam) to disclose its intracellular distribution using osmium as an intrinsic reporter. High resolution mapping of the lipophilic Oc-OH-Tam in cells, revealed its preferential accumulation in the endomembrane system encompassing endoplasmic reticulum,nuclear envelope and vesicular structures. This is consistent with the ability of the amino nitrogen chain of the compounds to be protonated at physiological pH and responsible for electrostatic interactions between Oc-OH-Tam and membranes. We propose a comprehensive scenario that provides new insight into the cellular behavior and activation of Oc-OH-Tam and advances the understanding of its mechanism of action.

Published
2019
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30. 3D histopathology speckle phase contrast imaging: from synchrotron to conventional sources

Author

Pierre Lhuissier, Olivier Stephanov, Sam Bayat, Ludovic Broche, Barbara Fayard, Sebastien Berujon, Emmanuel Brun, David M. Paganin, Luc Salvo, Hélène Labriet, Sylvain Bohic, Science et Ingénierie des Matériaux et Procédés (SIMaP ), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Ludwig Maximilians Univ Munchen, Dept Phys, D-85748 Garching, Germany, European Synchrotron Radiation Facility (ESRF), Centre de Recherche sur les Matériaux d'Intérêt Biologique, Université de Nantes (UN)-UPRES EA 2159, Université Grenoble Alpes - UFR Médecine (UGA UFRM), and Université Grenoble Alpes [2016-2019] (UGA [2016-2019])

Subjects
Image quality, business.industry, Computer science, Phase (waves), Phase-contrast imaging, Field of view, Gold standard (test), 01 natural sciences, Synchrotron, 030218 nuclear medicine & medical imaging, law.invention, 03 medical and health sciences, Speckle pattern, 0302 clinical medicine, law, 0103 physical sciences, Computer vision, Artificial intelligence, [PHYS.PHYS.PHYS-INS-DET]Physics [physics]/Physics [physics]/Instrumentation and Detectors [physics.ins-det], 010306 general physics, Phase retrieval, business, ComputingMilieux_MISCELLANEOUS
Abstract

Standard histopathological examination is the gold standard for many disease diagnoses although the technique is limited with no full 3D volume analysis possible. Three dimensional X-ray Phase-Contrast Imaging(PCI) methods have been under constant and fast developments in the recent decades due to their superior performance for imaging low density objects and their ability to provide complementary information compared to attenuation based imaging. Despite the progresses, X-ray Phase Contrast Tomography still encounters remaining challenges to overcome on its way to become a routine non-invasive technique allowing the 3D assessment of tissue architecture in laboratory set-ups. Speckle Based Imaging (SBI) forms a new class of X-ray PCI techniques, sensitive to the first derivative of the phase. The set-up involved and the simplicity of implementation provide many advantages to SBI such as having no field of view and no resolution limitation in addition to have low requirements on the beam coherences. These advantages make SBI a good candidate for the transfer on conventional sources. In this work, we present preliminary results obtained on a conventional μCT and their comparison with data acquired at the European Synchrotron. We used a new phase retrieval algorithm based on optical energy conservation. We applied the method on both phantoms and biological samples in order to evaluate its quantitativeness for a transfer. A comparison to previously available speckle tracking algorithms is also performed. We demonstrate that the combination of the phase retrieval method with a standard μCT can achieve high resolution and high contrast within a few minutes, with a comparable image quality to the results obtained using synchrotron light.

Published
2019
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31. Unsupervised solution for in-line holography phase retrieval using Bayesian inference

Author

Florin, Fus, Yang, Yang, Alexandra, Pacureanu, Sylvain, Bohic, and Peter, Cloetens

Abstract

In propagation based phase contrast imaging, intensity patterns are recorded on a x-ray detector at one or multiple propagation distances, called in-line holograms. They form the input of an inversion algorithm that aims at retrieving the phase shift induced by the object. The problem of phase retrieval in in-line holography is an ill-posed inverse problem. Consequently an adequate solution requires some form of regularization with the most commonly applied being the classical Tikhonov regularization. While generally satisfying this method suffers from a few issues such as the choice of the regularization parameter. Here, we offer an alternative to the established method by applying the principles of Bayesian inference. We construct an iterative optimization algorithm capable of both retrieving the unknown phase and determining a multi-dimensional regularization parameter. In the end, we highlight the advantages of the introduced algorithm, chief among them being the unsupervised determination of the regularization parameter(s). The proposed approach is tested on both simulated and experimental data and is found to provide robust solutions, with improved response to typical issues like low frequency noise and the twin-image problem.

Published
2019

32. Sub-ppm level high energy resolution fluorescence detected X-ray absorption spectroscopy of selenium in articular cartilage

Author

Ilyas M. Khan, Sylvain Bohic, Lenny H. E. Winkel, C. Bissardon, Jean-Louis Hazemann, Lewis Francis, Laurent Charlet, Olivier Proux, Sarah Bureau, Elke Suess, R.S. Conlan, Institut des Sciences de la Terre (ISTerre), Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-PRES Université de Grenoble-Institut de recherche pour le développement [IRD] : UR219-Institut national des sciences de l'Univers (INSU - CNRS)-Institut Français des Sciences et Technologies des Transports, de l'Aménagement et des Réseaux (IFSTTAR)-Université Joseph Fourier - Grenoble 1 (UJF), School of Medicine, Swansea University, Observatoire des Sciences de l'Univers de Grenoble (OSUG), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Institute of Biogeochemistry and Pollutant Dynamics [ETH Zürich] (IBP), Department of Environmental Systems Science [ETH Zürich] (D-USYS), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology in Zürich [Zürich] (ETH Zürich)-Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology in Zürich [Zürich] (ETH Zürich), MRS - Matériaux, Rayonnements, Structure, Institut Néel (NEEL), Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Rayonnement Synchrotron et Recherche Medicale (RSRM), Université Joseph Fourier - Grenoble 1 (UJF)-European Synchrotron Radiation Facility (ESRF)-Institut National de la Santé et de la Recherche Médicale (INSERM), European Synchrotron Radiation Facility (ESRF), ANR-10-LABX-0056/10-LABX-0056,OSUG@2020,Innovative strategies for observing and modelling natural systems(2010), ANR-13-BS08-0012,DyStrAS,Structure & Dynamique des Alumino-Silicates Fondus(2013), ANR-10-EQPX-27-01,EcoX,Ligne de lumière microfocus et très haute dilution à l'ESRF pour les sciences de l'environnement, Institut Français des Sciences et Technologies des Transports, de l'Aménagement et des Réseaux (IFSTTAR)-Institut national des sciences de l'Univers (INSU - CNRS)-Institut de recherche pour le développement [IRD] : UR219-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Observatoire des Sciences de l'Univers de Grenoble (OSUG ), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut national des sciences de l'Univers (INSU - CNRS)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich)- Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Matériaux, Rayonnements, Structure (MRS), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), ANR-10-LABX-0056,OSUG@2020,Innovative strategies for observing and modelling natural systems(2010), ANR-10-EQPX-0027,EcoX,Ligne de lumière microfocus et très haute dilution à l'ESRF pour les sciences de l'environnement(2010), Matériaux, Rayonnements, Structure (NEEL - MRS), and European Synchrotron Radiation Facility (ESRF)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Cartilage, Articular, Male, Materials science, Absorption spectroscopy, Resolution (mass spectrometry), [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, media_common.quotation_subject, Analytical chemistry, chemistry.chemical_element, Articular cartilage, 02 engineering and technology, 01 natural sciences, Biochemistry, Fluorescence, Analytical Chemistry, Crystal, Selenium, Limit of Detection, Electrochemistry, Animals, Humans, Environmental Chemistry, Least-Squares Analysis, Spectroscopy, media_common, Principal Component Analysis, X-ray absorption spectroscopy, 010401 analytical chemistry, 021001 nanoscience & nanotechnology, 0104 chemical sciences, Speciation, X-Ray Absorption Spectroscopy, chemistry, Cattle, 0210 nano-technology
Abstract

International audience; The speciation of highly-diluted elements by X-ray absorption spectroscopy in a diverse range of materials is extremely challenging, especially in biological matrices such as articular cartilage. Here we show that using a high energy resolution fluorescence detected X-ray absorption spectroscopy (HERFD-XAS) technique coupled to an array of crystal analyzers, selenium speciation down to 400 ppb (μg/kg) within articular cartilage can be demonstrated. This is a major advance in the speciation of highly-diluted elements through X-ray absorption spectroscopy and opens new possibilities to study the metabolic role of selenium and other elements in biological samples.

Published
2019
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33. Overcoming the challenges of high-energy X-ray ptychography

Author

Marie Ruat, Cyril Ponchut, Jean Claude Labiche, O. Hignette, Alexandra Pacureanu, Cyril Guilloud, Yang Yang, Murielle Salomé, Christophe Jarnias, Sylvain Bohic, Peter Cloetens, Julio Cesar da Silva, Matériaux, Rayonnements, Structure (MRS), Institut Néel (NEEL), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), and European Synchrotron Radiation Facility (ESRF)

Subjects
Diffraction, Nuclear and High Energy Physics, X-ray ptychography, Optics and Photonics, Materials science, Astrophysics::High Energy Astrophysical Phenomena, coherent X-ray diffraction, 02 engineering and technology, 01 natural sciences, law.invention, 010309 optics, Speckle pattern, Optics, X-Ray Diffraction, law, 0103 physical sciences, [PHYS.PHYS.PHYS-INS-DET]Physics [physics]/Physics [physics]/Instrumentation and Detectors [physics.ins-det], nano-imaging, high-energy X-rays, Instrumentation, Lithography, [PHYS]Physics [physics], Radiation, business.industry, X-Rays, Equipment Design, Models, Theoretical, 021001 nanoscience & nanotechnology, Coherent diffraction imaging, KB mirrors, Synchrotron, Ptychography, coherence, Radiographic Image Enhancement, Beamline, High-energy X-rays, [SPI.OPTI]Engineering Sciences [physics]/Optics / Photonic, Gold, 0210 nano-technology, business, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, Synchrotrons
Abstract

International audience; X-ray ptychography is a coherent diffraction imaging technique with a high resolving power and excellent quantitative capabilities. Although very popular in synchrotron facilities nowadays, its implementation with X-ray energies above 15 keV is very rare due to the challenges imposed by the high energies. Here, the implementation of high-energy X-ray ptychography at 17 and 33.6 keV is demonstrated and solutions to overcome the important challenges are provided. Among the particular aspects addressed are the use of an efficient high-energy detector, a long synchrotron beamline for the high degree of spatial coherence, a beam with 1% monochromaticity providing high flux, and efficient multilayer coated Kirkpatrick-Baez X-ray optics to shape the beam. The constraints imposed by the large energy bandwidth are carefully analyzed, as well as the requirements to sample correctly the high-energy diffraction patterns with small speckle size. In this context, optimized scanning trajectories allow the total acquisition time to be reduced by up to 35%. The paper explores these innovative solutions at the ID16A nano-imaging beamline by ptychographic imaging of a 200 nm-thick gold lithography sample.

Published
2018
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34. Comparison of X-ray speckle-based imaging deflection retrieval algorithms for the optimization of radiation dose

Author

Laurène Quénot, Sylvain Bohic, David M. Paganin, Emmanuel Brun, Sebastien Berujon, Hélène Rougé-Labriet, and Barbara Fayard

Subjects
Quality Control, Computer science, Optical flow, Radiation Dosage, 030218 nuclear medicine & medical imaging, law.invention, 03 medical and health sciences, Speckle pattern, 0302 clinical medicine, Optics, law, Humans, Microscopy, Phase-Contrast, Radiology, Nuclear Medicine and imaging, Sensitivity (control systems), Radiometry, Observer Variation, Radiological and Ultrasound Technology, Phantoms, Imaging, business.industry, X-Rays, Attenuation, Phase-contrast imaging, Equipment Design, Synchrotron, Radiography, 030220 oncology & carcinogenesis, X-Ray Phase-Contrast Imaging, business, Phase retrieval, Algorithms, Synchrotrons
Abstract

X-ray phase contrast imaging can provide improved or complementary information to traditional attenuation-based X-ray imaging, making the field a vast and rapidly evolving research subject. X-ray speckle-based imaging (SBI) is one phase-contrast imaging approach that has shown significant potential in providing both high sensitivity and high resolution while using a very simple experimental setup. With the aim of transferring such phase-contrast-based imaging techniques from synchrotron to laboratory X-ray sources, the issue of the deposited radiation dose still remains to be addressed. In this work, we experimentally and quantitatively compare the results from three different SBI phase retrieval algorithms using both phantoms and biological samples in order to infer the optimal configuration. The results obtained using a synchrotron beam suggest that the technique based on optical flow conservation achieves the most accurate retrieval from the lowest number of sample exposures. This constitutes an important step toward the possibility of transferring SBI into the clinic.

Published
2021
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35. Synchrotron Radiation X-Ray Fluorescence Nanoimaging Reveal the Intracellular Localization of Potent Anticancer Drug Osmocenyl-Tamoxifen Derivative

Author

Gérard Jaouen, Julio Cesar da Silva, Sylvain Bohic, Anne Vessiere, Alexandra Pacureanu, Hui Zhi Shirley Lee, Peter Cloetens, Michèle Salmain, Marie Carrière, Yang Yang, Siden Top, Florin Fus, Alexandre Bouron, European Synchrotron Radiation Facility (ESRF), Institut Parisien de Chimie Moléculaire (IPCM), Chimie Moléculaire de Paris Centre (FR 2769), Université Pierre et Marie Curie - Paris 6 (UPMC)-ESPCI ParisTech-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris)-Université Pierre et Marie Curie - Paris 6 (UPMC)-ESPCI ParisTech-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Chimie Interface Biologie pour l’Environnement, la Santé et la Toxicologie (CIBEST), SYstèmes Moléculaires et nanoMatériaux pour l’Energie et la Santé (SYMMES), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Laboratoire de Chimie et Biologie des Métaux (LCBM - UMR 5249), European Programme for Intervention Epidemiology Training (EPIET), European Centre for Disease Prevention and Control (ECDC), Institut de Chimie du CNRS (INC)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Chimie Interface Biologie pour l’Environnement, la Santé et la Toxicologie (CIBEST ), Institut de Chimie du CNRS (INC)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Chemical Biology (CHEMBIO), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Chimie Moléculaire de Paris Centre (FR 2769), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL), and European Centre for Disease Prevention and Control [Stockholm, Sweden] (ECDC)

Subjects
0301 basic medicine, Intracellular localization, Synchrotron radiation, X-ray fluorescence, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, Anticancer drug, 3. Good health, 03 medical and health sciences, chemistry.chemical_compound, 030104 developmental biology, 0302 clinical medicine, chemistry, 030220 oncology & carcinogenesis, medicine, Biophysics, Instrumentation, Derivative (chemistry), Tamoxifen, ComputingMilieux_MISCELLANEOUS, medicine.drug
Abstract

International audience

Published
2018
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36. Nanoscale three-dimensional imaging of biological tissue with x-ray holographic tomography

Author

Julio Caesar da Silva, Sylvain Bohic, Alexandra Pacureanu, Peter Cloetens, and Yang Yang

Subjects
Materials science, Three dimensional imaging, law, Phase contrast microscopy, Microscopy, Deep penetration, Holography, Nanotechnology, Tomography, Biological tissue, Nanoscopic scale, law.invention
Abstract

Enabling exploration of biological tissue in three-dimensions at sub-cellular scale is instrumental for advancing our understanding of biological systems and for finding better ways to cope with diseases. Over the last few years, remarkable advances in microscopy facilitated probing cells and tissues at the nanometer scale but many limitations are yet to be overcome. Here we present a novel technique which enables label-free volume imaging of biological tissue with pixel sizes down to 25 nm while maintaining extensive sample coverage. X-ray holographic nanotomography is a full-field 3D imaging technique which benefits from the deep penetration of X-rays and the powerful mechanism of phase contrast. By using cryogenic sample preservation, the tissue can be investigated close to the native state. The unprecedented data created by this technique opens new avenues in life sciences research.

Published
2018
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37. Nanoscopic X-ray fluorescence imaging and quantification of intracellular key-elements in cryofrozen Friedreich’s ataxia fibroblasts

Author

Rudy Van Coster, Eline Meul, Brecht Laforce, Björn De Samber, Peter Cloetens, Peter Vandenabeele, Michiel De Bruyne, Riet De Rycke, Sylvain Bohic, Joél Smet, Boel De Paepe, Tom Vanden Berghe, Universiteit Gent = Ghent University [Belgium] (UGENT), VIB-UGent Center for Inflammation Research [Gand, Belgique] (IRC), VIB [Belgium], Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), European Synchrotron Radiation Facility (ESRF), ORANGE, Colette, and Universiteit Gent = Ghent University (UGENT)

Subjects
0301 basic medicine, Cytoplasm, Luminescence, Glaciology, [SDV]Life Sciences [q-bio], Synchrotron radiation, lcsh:Medicine, PROTEIN, COPPER, Negative Staining, YEAST FRATAXIN, ZINC, 0302 clinical medicine, Limit of Detection, Animal Cells, Ice Cores, Medicine and Health Sciences, Group-Specific Staining, Nanotechnology, OXIDATIVE STRESS, lcsh:Science, Chemical composition, Connective Tissue Cells, Staining, Multidisciplinary, Chemistry, IRON, Physics, Electromagnetic Radiation, Reference Standards, Fluorescence, [SDV] Life Sciences [q-bio], DEFICIENCY, Zinc, medicine.anatomical_structure, Connective Tissue, Physical Sciences, LIBRARY, Prussian Blue Staining, Cellular Types, Anatomy, Cellular Structures and Organelles, Elementary Particles, Research Article, Chemical Elements, Iron, chemistry.chemical_element, X-ray fluorescence, Research and Analysis Methods, 03 medical and health sciences, REDISTRIBUTION, medicine, Humans, Fibroblast, Particle Physics, Nanoscopic scale, Cryopreservation, Photons, CARDIOMYOPATHY, lcsh:R, Spectrometry, X-Ray Emission, Correction, Biology and Life Sciences, Cell Biology, Fibroblasts, 030104 developmental biology, Biological Tissue, Friedreich Ataxia, Specimen Preparation and Treatment, Biophysics, Earth Sciences, lcsh:Q, 030217 neurology & neurosurgery
Abstract

International audience; Synchrotron radiation based nanoscopic X-ray fluorescence (SR nano-XRF) analysis can visualize trace level elemental distribution in a fully quantitative manner within single cells. However, in-air XRF analysis requires chemical fixation modifying the cell's chemical composition. Here, we describe first nanoscopic XRF analysis upon cryogenically frozen (-150 degrees C) fibroblasts at the ID16A-NI 'Nano-imaging' end-station located at the European Synchrotron Radiation Facility (ESRF) in Grenoble (France). Fibroblast cells were obtained from skin biopsies from control and Friedreich's ataxia (FRDA) patients. FRDA is an autosomal recessive disorder with dysregulation of iron metabolism as a key feature. By means of the X-ray Fundamental Parameter (FP) method, including absorption correction of the ice layer deposited onto the fibroblasts, background-corrected mass fraction elemental maps of P, S, Cl, K, Ca, Fe and Zn of entire cryofrozen human fibroblasts were obtained. Despite the presence of diffracting microcrystals in the vitreous ice matrix and minor sample radiation damage effects, clusters of iron-rich hot-spots with similar mass fractions were found in the cytoplasm of both control and FRDA fibroblasts. Interestingly, no significant difference in the mean iron concentration was found in the cytoplasm of FRDA fibroblasts, but a significant decrease in zinc concentration. This finding might underscore metal dysregulation, beyond iron, in cells derived from FRDA patients. In conclusion, although currently having slightly increased limits of detection (LODs) compared to non-cryogenic mode, SR based nanoscopic XRF under cryogenic sample conditions largely obliterates the debate on chemical sample preservation and provides a unique tool for trace level elemental imaging in single cells close to their native state with a superior spatial resolution of 20 nm.

Published
2018
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38. Nanoscale quantification of intracellular element concentration by X-ray fluorescence microscopy combined with X-ray phase contrast nanotomography

Author

Yang Yang, Chiara Gramaccioni, Sylvain Bohic, Stefano Lagomarsino, Giovanna Farruggia, Alessandra Procopio, Emil Malucelli, Peter Cloetens, Piera Valenti, Luigi Rosa, Andrea Notargiacomo, Stefano Iotti, Inna Bukreeva, Alexandra Pacureanu, Francesca Berlutti, Michela Fratini, Gramaccioni, Chiara, Yang, Yang, Procopio, Alessandra, Pacureanu, Alexandra, Bohic, Sylvain, Malucelli, Emil, Iotti, Stefano, Farruggia, Giovanna, Bukreeva, Inna, Notargiacomo, Andrea, Fratini, Michela, Valenti, Piera, Rosa, Luigi, Berlutti, Francesca, Cloetens, Peter, and Lagomarsino, Stefano

Subjects
0301 basic medicine, Molar concentration, Materials science, Physics and Astronomy (miscellaneous), X-ray, Analytical chemistry, Synchrotron radiation, X-ray fluorescence, cell, Cell morphology, 03 medical and health sciences, 030104 developmental biology, x ray fluorescence, chemical analysis, Microscopy, atomic-force microscopy, fluorescence, cells, Fluorescence microscope, x ray phase contrast tomography, Nanoscopic scale
Abstract

We present here a correlative X-ray microscopy approach for quantitative single cell imaging of molar concentrations. By combining the elemental content provided by X-ray fluorescence microscopy and the morphology information extracted from X-ray phase nanotomography, we determine the intracellular molarity distributions. This correlative method was demonstrated on a freeze-dried human phagocytic cell to obtain the absolute elemental concentration maps of K, P, and Fe. The cell morphology results showed a very good agreement with atomic-force microscopy measurements. This work opens the way for non-destructive single cell chemical analysis down to the sub-cellular level using exclusively synchrotron radiation techniques. It will be of high interest in the case where it is difficult to access the morphology using atomic-force microscopy, for example, on frozen-hydrated cells or tissues.

Published
2018
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39. Zinc and Copper Effects on Stability of Tubulin and Actin Networks in Dendrites and Spines of Hippocampal Neurons

Author

Jennifer D. Petersen, Asuncion Carmona, Stéphane Roudeau, Richard Ortega, Peter Cloetens, Sylvain Bohic, Florelle Domart, Laura Perrin, Yang Yang, Centre d'Etudes Nucléaires de Bordeaux Gradignan (CENBG), Université Sciences et Technologies - Bordeaux 1-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), European Synchrotron Radiation Facility (ESRF), [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Grenoble Institut des Neurosciences (GIN), and Université Joseph Fourier - Grenoble 1 (UJF)-Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
0301 basic medicine, Dendritic spine, Physiology, Cognitive Neuroscience, chemistry.chemical_element, Fluorescent Antibody Technique, Dermoscopy, Zinc, macromolecular substances, Hippocampal formation, Biochemistry, Hippocampus, Rats, Sprague-Dawley, 03 medical and health sciences, 0302 clinical medicine, Microtubule, Tubulin, Cations, medicine, Animals, Cytoskeleton, Cells, Cultured, Chelating Agents, [PHYS]Physics [physics], Spectrometry, X-Ray Emission, Cell Biology, General Medicine, Dendrites, Copper Chelation, Copper, Actins, Coculture Techniques, 030104 developmental biology, medicine.anatomical_structure, chemistry, Astrocytes, Biophysics, Neuron, 030217 neurology & neurosurgery
Abstract

International audience; Zinc and copper ions can modulate the activity of glutamate receptors. However, labile zinc and copper ions likely represent only the tip of the iceberg and other neuronal functions are suspected for these metals in their bound state. We performed synchrotron X-ray fluorescence imaging with 30 nm resolution to image total biometals in dendrites and spines from hippocampal neurons. We found that zinc is distributed all along the dendrites while copper is mainly pinpointed within the spines. In spines, zinc content is higher within the spine head while copper is higher within the spine neck. Such specific distributions suggested metal interactions with cytoskeleton proteins. Zinc supplementation induced the increase of β-tubulin content in dendrites. Copper supplementation impaired the β-tubulin and F-actin networks. Copper chelation resulted in the decrease of F-actin content in dendrites, drastically reducing the number of F-actin protrusions. These results indicate that zinc is involved in microtubule stability whereas copper is essential for actin-dependent stability of dendritic spines, although copper excess can impair the dendritic cytoskeleton.

Published
2017
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40. High-energy cryo x-ray nano-imaging at the ID16A beamline of ESRF

Author

Sylvain Bohic, Julio Cesar da Silva, Peter Cloetens, Maxime Hubert, Florin Fus, Leonid Bloch, Murielle Salomé, Yang Yang, Alexandra Pacureanu, DA SILVA, Julio, European Synchroton Radiation Facility [Grenoble] (ESRF), Groupe Physiopathologie du Cytosquelette (GPC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)

Subjects
[PHYS.PHYS.PHYS-OPTICS] Physics [physics]/Physics [physics]/Optics [physics.optics], Photon, Materials science, Nanoprobe, X-ray fluorescence, 02 engineering and technology, x-ray fluorescence imaging, 01 natural sciences, 010309 optics, Optics, 0103 physical sciences, Nano, [PHYS.PHYS.PHYS-INS-DET]Physics [physics]/Physics [physics]/Instrumentation and Detectors [physics.ins-det], high-energy X-rays, [PHYS.PHYS.PHYS-OPTICS]Physics [physics]/Physics [physics]/Optics [physics.optics], business.industry, X-ray, nanofocusing, 021001 nanoscience & nanotechnology, KB mirrors, [PHYS.COND.CM-MS] Physics [physics]/Condensed Matter [cond-mat]/Materials Science [cond-mat.mtrl-sci], Characterization (materials science), coherent x-ray imaging, Beamline, [PHYS.PHYS.PHYS-INS-DET] Physics [physics]/Physics [physics]/Instrumentation and Detectors [physics.ins-det], High-energy X-rays, nanoimaging, nanoprobe, [PHYS.COND.CM-MS]Physics [physics]/Condensed Matter [cond-mat]/Materials Science [cond-mat.mtrl-sci], 0210 nano-technology, business, synchrotron beamline
Abstract

International audience; The ID16A beamline at ESRF offers unique capabilities for X-ray nano-imaging, and currently produces the worlds brightest high energy diffraction-limited nanofocus. Such a nanoprobe was designed for quantitative characterization of the morphology and the elemental composition of specimens at both room and cryogenic temperatures. Billions of photons per second can be delivered in a diffraction-limited focus spot size down to 13 nm. Coherent X-ray imaging techniques, as magnified holographic-tomography and ptychographic-tomography, are implemented as well as X-ray fluorescence nanoscopy. We will show the latest developments in coherent and spectroscopic X-ray nanoimaging implemented at the ID16A beamline.

Published
2017
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41. Impact of manganese on primary hippocampal neurons from rodents

Author

Yasmina Saoudi, Sylvain Bohic, Annie Andrieux, Mariano Bisbal, Jacques Brocard, Emmanuel L. Barbier, Alexia Daoust, Murielle Salomé, Nora Collomb, and Cécile Batandier

Subjects
0303 health sciences, Cell type, Chemistry, Cognitive Neuroscience, Cell, Neurotoxicity, Mitochondrion, Hippocampal formation, medicine.disease, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, Mitochondrial permeability transition pore, In vivo, medicine, Biophysics, Neuroscience, Incubation, 030217 neurology & neurosurgery, 030304 developmental biology
Abstract

Manganese-enhanced magnetic resonance imaging (MEMRI) is a powerful tool for in vivo tract tracing or functional imag- ing of the central nervous system. However Mn 21 may be toxic at high levels. In this study, we addressed the impact of Mn 21 on mouse hippo- campal neurons (HN) and neuron-like N2a cells in culture, using several approaches. Both HN and N2a cells not exposed to exogenous MnCl2 were shown by synchrotron X-ray fluorescence to contain 5 mg/g Mn. Concentrations of Mn 21 leading to 50% lethality (LC50) after 24 h of incubation were much higher for N2a cells (863 mM) than for HN (90 mM). The distribution of Mn 21 in both cell types exposed to Mn 21 concentrations below LC50 was perinuclear whereas that in cells exposed to concentrations above LC50 was more diffuse, suggesting an overloading of cell storage/detoxification capacity. In addition, Mn 21 had a cell-type and dose-dependent impact on the total amount of intra- cellular P, Ca, Fe and Zn measured by synchrotron X-ray fluorescence. For HN neurons, immunofluorescence studies revealed that concentra- tions of Mn 21 below LC50 shortened neuritic length and decreased mitochondria velocity after 24 h of incubation. Similar concentrations of Mn 21 also facilitated the opening of the mitochondrial permeability transition pore in isolated mitochondria from rat brains. The sensitivity of primary HN to Mn 21 demonstrated here supports their use as a rele- vant model to study Mn 21 -induced neurotoxicity. V C 2014 Wiley

Published
2014
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42. High Resolution X-Ray Phase Contrast Imaging of Maturating Cartilage

Author

Emmanuel Brun, Laurent Charlet, Hervé Mathieu, Hélène Labriet, Caroline Bissardon, Ilyas M. Khan, Sebastien Berujon, and Sylvain Bohic

Subjects
medicine.anatomical_structure, Materials science, Nuclear magnetic resonance, X-Ray Phase-Contrast Imaging, Cartilage, medicine, High resolution, Instrumentation
Published
2018
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43. Quantitative Nano-imaging of Cells with a High Energy X-ray Cryo Nano-probe

Author

Sylvain Bohic, Alexandra Pacureanu, Peter Cloetens, Murielle Salomé, Florin Fus, Yang Yang, and Julio Cesar da Silva

Subjects
010302 applied physics, Materials science, 0103 physical sciences, Nano, X-ray, Nanotechnology, 02 engineering and technology, 021001 nanoscience & nanotechnology, 0210 nano-technology, 01 natural sciences, Instrumentation, Energy (signal processing)
Published
2018
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45. ID16B: a hard X-ray nanoprobe beamline at the ESRF for nano-analysis

Author

R. Baker, John Morse, Cyril Guilloud, Gema Martínez-Criado, Sylvain Labouré, Yves Dabin, Rémi Tucoulou, Sylvain Bohic, E. Gagliardini, Cédric Cohen, Valentin Valls, Julie Villanova, Damien Salomon, Jussi-Petteri Suuronen, and Raymond Barrett

Subjects
0301 basic medicine, Diffraction, 030103 biophysics, Nuclear and High Energy Physics, X-ray nanoprobe, X-ray fluorescence, 02 engineering and technology, law.invention, 03 medical and health sciences, Optics, law, Instrumentation, Image resolution, Microspectroscopy, Radiation, business.industry, Beamlines, Undulator, 021001 nanoscience & nanotechnology, Synchrotron, Upgrade, FRELON CAMERA, Beamline, 0210 nano-technology, business
Abstract

ID16B is a versatile hard X-ray nanoprobe devoted to X-ray nano-analysis. It combines X-ray fluorescence, X-ray diffraction, X-ray absorption spectroscopy and 2D/3D X-ray imaging techniques., Within the framework of the ESRF Phase I Upgrade Programme, a new state-of-the-art synchrotron beamline ID16B has been recently developed for hard X-ray nano-analysis. The construction of ID16B was driven by research areas with major scientific and societal impact such as nanotechnology, earth and environmental sciences, and bio-medical research. Based on a canted undulator source, this long beamline provides hard X-ray nanobeams optimized mainly for spectroscopic applications, including the combination of X-ray fluorescence, X-ray diffraction, X-ray excited optical luminescence, X-ray absorption spectroscopy and 2D/3D X-ray imaging techniques. Its end-station re-uses part of the apparatus of the earlier ID22 beamline, while improving and enlarging the spectroscopic capabilities: for example, the experimental arrangement offers improved lateral spatial resolution (∼50 nm), a larger and more flexible capability for in situ experiments, and monochromatic nanobeams tunable over a wider energy range which now includes the hard X-ray regime (5–70 keV). This paper describes the characteristics of this new facility, short-term technical developments and the first scientific results.

Published
2016

46. Deciphering the Resistance-Counteracting Functions of Ferroquine in Plasmodium falciparum-Infected Erythrocytes

Author

Faustine Dubar, Jamal Khalife, Christophe Biot, Yann Guérardel, Peter Cloetens, Daniel Dive, and Sylvain Bohic

Subjects
Drug resistance, Vacuole, Pharmacology, 010402 general chemistry, 01 natural sciences, Biochemistry, Aminoquinoline, 03 medical and health sciences, Chloroquine, Drug Discovery, medicine, 030304 developmental biology, 0303 health sciences, biology, business.industry, Organic Chemistry, Plasmodium falciparum, medicine.disease, biology.organism_classification, Antiparasitic agent, Virology, 0104 chemical sciences, 3. Good health, Efflux, business, Malaria, medicine.drug
Abstract

The aminoquinoline chloroquine (CQ) has been widely used for treating malaria since World War II. Resistance to CQ began to spread around 1957 and is now found in all malarious areas of the world. CQ resistance is caused by multiple mutations in the Plasmodium falciparum chloroquine resistance transporter (PfCRT). These mutations result in an increased efflux of CQ from the acidic digestive vacuole (DV) to the cytosol of the parasite. This year, we proposed a strategy to locate and quantify the aminoquinolines in situ within infected red blood cells (iRBCs) using synchrotron based X-ray nanoprobe fluorescence. Direct measurements of unlabeled CQ and ferroquine (FQ) (a ferrocene-CQ conjugate, extremely active against CQ-resistant strains) enabled us to evidence fundamentally different transport mechanisms from the cytosol to the DV between CQ and FQ in the CQ-susceptible strain HB3. These results inspired the present study of the localization of CQ and FQ in the CQ-resistant strain W2. The introduction of the ferrocene core in the lateral side chain of CQ has an important consequence: the transporter is unable to efflux FQ from the DV. We also found that resistant parasites treated by FQ accumulate a sulfur-containing compound, credibly glutathion, in their DV.

Published
2012
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47. Status of the hard X-ray microprobe beamline ID22 of the European Synchrotron Radiation Facility

Author

Juan Angel Sans, Rémi Tucoulou, Gema Martínez-Criado, Alexander Rack, Sylvain Petitgirard, Jean Cauzid, J. Segura-Ruiz, Heikki Suhonen, Julie Villanova, Peter Cloetens, Ewelina Kosior, Jean Susini, Pierre Bleuet, Isabelle Kieffer, Sylvain Labouré, and Sylvain Bohic

Subjects
Nuclear and High Energy Physics, X-ray nanoprobe, medicine.medical_specialty, Materials science, Arsenites, Golgi Apparatus, Synchrotron radiation, law.invention, Cytosol, Optics, law, medicine, Humans, Medical physics, Instrumentation, Cell Nucleus, Manganese, Radiation, business.industry, X-Rays, Spectrometry, X-Ray Emission, Hep G2 Cells, Synchrotron, Mitochondria, X-Ray Absorption Spectroscopy, Upgrade, Beamline, X ray microprobe, Nanoparticles, business, Synchrotrons, DNA Damage, Electron Probe Microanalysis
Abstract

The ESRF synchrotron beamline ID22, dedicated to hard X-ray microanalysis and consisting of the combination of X-ray fluorescence, X-ray absorption spectroscopy, diffraction and 2D/3D X-ray imaging techniques, is one of the most versatile instruments in hard X-ray microscopy science. This paper describes the present beamline characteristics, recent technical developments, as well as a few scientific examples from recent years of the beamline operation. The upgrade plans to adapt the beamline to the growing needs of the user community are briefly discussed.

Published
2011
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48. Rôles biologiques des éléments traces dans le cerveau – exemples du Zn et du Fe

Author

Josiane Arnaud, Alexandre Bouron, Stéphane Hunot, Jean-François Ghersi-Egea, Julien Gibon, Pierre Paoletti, Sylvain Bohic, and Alain Boom

Subjects
0303 health sciences, Brain chemistry, Chemistry, Nervous tissue, Neurodegeneration, Neurotransmitter synthesis, Neurotransmission, medicine.disease, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, Neurology, medicine, Neurology (clinical), Neuroscience, 030217 neurology & neurosurgery, Homeostasis, 030304 developmental biology
Abstract

INTRODUCTION: Many metals like iron (Fe), copper (Cu) or zinc (Zn) fulfil various essential biological functions and are thus vital for all living organisms. For instance, they play important roles in nervous tissue, participating in a wide range of processes such as neurotransmitter synthesis, myelination or synaptic transmission. STATE OF THE ART: As in other tissues, brain cells tightly control the concentration of metals but any excess or deficit can lead to deleterious responses and alter cognitive functions. Of note, certain metals such as Zn, Fe or Cu accumulate in specific brain structures over lifespan and several neurodegenerative diseases are associated with a dysregulation of the homeostatic mechanisms controlling the concentration of these cations. CONCLUSION AND PERSPECTIVES: This review will address some of the cellular and molecular processes controlling the entry and distribution of selected metals (mainly Zn and Fe) in the brain, as well as their roles in synaptic transmission, in the pathogenesis of some neurologic diseases such as Parkinson's disease and Alzheimer's disease, and their impact on cognitive functions.

Published
2011
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49. Leukemia Inhibitory Factor and Oncostatin M Influence the Mineral Phases Formed in a Murine Heterotopic Calcification Model: A Fourier Transform-Infrared Microspectroscopic Study

Author

S. Touchais, Anne Godard, Ramin Rohanizadeh, Sylvain Bohic, G. Daculsi, and Dominique Heymann

Subjects
Transplantation, Heterotopic, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Bone Marrow Cells, Oncostatin M, Kidney, Leukemia Inhibitory Factor, Bone remodeling, Extracellular matrix, Mice, Spectroscopy, Fourier Transform Infrared, medicine, Animals, Orthopedics and Sports Medicine, Cells, Cultured, Bone Marrow Transplantation, Bone mineral, Lymphokines, Minerals, biology, Interleukin-6, Chemistry, Microchemistry, Calcinosis, medicine.disease, Growth Inhibitors, Cell biology, Radiography, Microscopy, Electron, Nephrocalcinosis, Cytokine, medicine.anatomical_structure, Immunology, Microscopy, Electron, Scanning, biology.protein, Female, Bone marrow, Peptides, Leukemia inhibitory factor, Calcification
Abstract

The study of bone mineralization processes is of considerable interest in understanding bone diseases and developing new therapies for skeletal disorders, particularly since bone homeostasis requires numerous cell types and a large cytokine network. Cell culture models of mineralization have often been used to study the cellular mechanisms of mineralization, but few data have been reported concerning the influence of extracellular matrix components and cytokines on the physicochemical properties of mineral. The purpose of this study was to analyze the effects of two cytokines, leukemia inhibitory factor (LIF) and oncostatin M (OSM), involved in bone metabolism on the physicochemical properties of bone mineral formed in a murine in vivo mineralization model. Murine bone marrow cells implanted under the kidney capsule in the presence or absence of cytokines led to heterotopic ossicle formation. A scanning electron microscopic microprobe revealed that heterotopic calcification had a lower (approximately 20%) Ca/P ratio after cytokine treatment as compared with the control without cytokine. Transmission electron microscopic analysis of cytokine-treated ossicles showed numerous areas with low mineral density, whereas electron diffraction pattern revealed an apatitic phase. These areas were not observed in the absence of cytokine. Moreover, Fourier transform-infrared microspectroscopy showed at the molecular level that the presence of either cytokine induced many microscopic areas in which short-range order organization, such as incorporation of carbonate and crystallinity/maturity of ossicle mineral, were modified. LIF and OSM influenced mineral phase formation in the present model and may thus be key protagonists in bone mineral development and skeletal diseases.

Published
2009
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50. State of the Art and Perspectives of Biomedical Imaging at the ESRF

Author

Paola Coan, José Baruchel, Alberto Bravin, Timm Weitkamp, Hélène Elleaume, Pierre Bleuet, Christian David, Françoise Peyrin, Pekka Suortti, François Estève, Franz Pfeiffer, Oliver Bunk, Sylvain Bohic, Baruchel, J, Bleuet, P, Bohic, S, Bravin, A, Coan, P, David, C, Elleaume, H, Esteve, F, Peyrin, F, Pfeiffer, F, Suortti, P, Bunk, O, and Weitkamp, T

Subjects
Physics, Nuclear and High Energy Physics, medicine.medical_specialty, Medical imaging, medicine, biomedical imaging, review, FIS/07 - FISICA APPLICATA (A BENI CULTURALI, AMBIENTALI, BIOLOGIA E MEDICINA), Medical physics, Atomic and Molecular Physics, and Optics
Abstract

The first practical application of X-rays, more than 100 years ago, was for biomedical imaging. Although not central to the initial development of 3 rd generation synchrotron light sources, imaging techniques have today established themselves as a core element of the research program at all major light sources, including the ESRF, where X-ray imaging has been identified as one of five main themes for its Upgrade Programme [1].

Published
2008
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