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1. IL-33-primed human mast cells drive IL-9 production by CD4+ effector T cells in an OX40L-dependent manner

Author: Louise Battut, Edouard Leveque, Salvatore Valitutti, Nicolas Cenac, Gilles Dietrich, and Eric Espinosa
Subjects: mast cell, IL-33, OX40L, Th cell, IL-9, Immunologic diseases. Allergy, RC581-607
Abstract: Interleukin-33 (IL-33) is an alarmin released by epithelial cells in response to tissue damage. It activates resident immune sentinel cells, which then produce signals commonly associated with type 2 immune responses, particularly affecting infiltrating antigen-specific T cells. Given that mast cells (MCs) are a primary target of IL-33 and can shape T helper (Th) cell responses, we investigated the effect of IL-33 priming on the ability of MCs to influence Th cell cytokine production. To examine the Th cell/MC interaction, we developed human primary MC/memory CD4+ T-cell coculture systems involving both cognate and non-cognate interactions. Our results demonstrated that IL-33-primed MCs, whether as bystander cells cocultured with activated effector T cells or functioning as antigen-presenting cells, promoted IL-9 and increased IL-13 production in Th cells via an OX40L-dependent mechanism. This indicates that MCs sense IL-33-associated danger, prompting them to direct Th cells to produce the key type 2 effector cytokines IL-9 and IL-13.
Published: 2024
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2. Enkephalin-mediated modulation of basal somatic sensitivity by regulatory T cells in mice

Author: Nicolas Aubert, Madeleine Purcarea, Julien Novarino, Julien Schopp, Alexis Audibert, Wangtianrui Li, Marie Fornier, Léonie Cagnet, Marie Naturel, Armanda Casrouge, Marie-Caroline Dieu-Nosjean, Nicolas Blanchard, Gilles Dietrich, Cedric Peirs, and Gilles Marodon
Subjects: pain, enkephalins, skin, immunoregulation, Medicine, Science, Biology (General), QH301-705.5
Abstract: CD4+CD25+Foxp3+ regulatory T cells (Treg) have been implicated in pain modulation in various inflammatory conditions. However, whether Treg cells hamper pain at steady state and by which mechanism is still unclear. From a meta-analysis of the transcriptomes of murine Treg and conventional T cells (Tconv), we observe that the proenkephalin gene (Penk), encoding the precursor of analgesic opioid peptides, ranks among the top 25 genes most enriched in Treg cells. We then present various evidence suggesting that Penk is regulated in part by members of the Tumor Necrosis Factor Receptor (TNFR) family and the transcription factor Basic leucine zipper transcription faatf-like (BATF). Using mice in which the promoter activity of Penk can be tracked with a fluorescent reporter, we also show that Penk expression is mostly detected in Treg and activated Tconv in non-inflammatory conditions in the colon and skin. Functionally, Treg cells proficient or deficient for Penk suppress equally well the proliferation of effector T cells in vitro and autoimmune colitis in vivo. In contrast, inducible ablation of Penk in Treg leads to heat hyperalgesia in both male and female mice. Overall, our results indicate that Treg might play a key role at modulating basal somatic sensitivity in mice through the production of analgesic opioid peptides.
Published: 2024
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3. Correction: Perinatal foodborne titanium dioxide exposure-mediated dysbiosis predisposes mice to develop colitis through life

Author: Caroline Carlé, Delphine Boucher, Luisa Morelli, Camille Larue, Ekaterina Ovtchinnikova, Louise Battut, Kawthar Boumessid, Melvin Airaud, Muriel Quaranta-Nicaise, Jean-Luc Ravanat, Gilles Dietrich, Sandrine Menard, Gérard Eberl, Nicolas Barnich, Emmanuel Mas, Marie Carriere, Ziad Al Nabhani, and Frédérick Barreau
Subjects: Toxicology. Poisons, RA1190-1270, Industrial hygiene. Industrial welfare, HD7260-7780.8
Published: 2024
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4. Thoracic spinous process nonunion as an unusual cause of back pain: a case report and review of the literature

Author: Gilles Dietrich, Raphaël Richard, Alain Akiki, Sebastien Levy, and Benoit Maeder
Subjects: Spinous process, Nonunion, Pseudoarthrosis, Resection, Case report, Medicine
Abstract: Abstract Background Purely isolated spinous processes fractures are rare and are usually treated conservatively, although a few authors have reported cases of nonunion that ultimately required surgical resection. Case presentation We present a case of an isolated T6 spinous process pseudoarthrosis that was treated by surgical resection of the tip of the spinous process. A 34-year-old Caucasian male patient was complaining of mid-thoracic back pain without neurologic impairment more than 2 years after an isolated spinous process fracture. Magnetic Resonance Imaging (MRI) and Single Photon Emission Computed Tomography (SPECT) revealed a nonunion. We performed a resection without further complication. Conclusion Although spinous process nonunions may in some cases be well tolerated, surgical resection appears to be a reliable option in case of persistent symptoms. This illustrated case shows the description of an isolated thoracic spinous process nonunion and its surgical treatment.
Published: 2024
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5. Perinatal foodborne titanium dioxide exposure-mediated dysbiosis predisposes mice to develop colitis through life

Author: Caroline Carlé, Delphine Boucher, Luisa Morelli, Camille Larue, Ekaterina Ovtchinnikova, Louise Battut, Kawthar Boumessid, Melvin Airaud, Muriel Quaranta-Nicaise, Jean-Luc Ravanat, Gilles Dietrich, Sandrine Menard, Gérard Eberl, Nicolas Barnich, Emmanuel Mas, Marie Carriere, Ziad Al Nabhani, and Frédérick Barreau
Subjects: Perinatal period, Foodborne TiO2, Intestinal barrier function, Intestinal stem cells, Microbiota, Colitis, Toxicology. Poisons, RA1190-1270, Industrial hygiene. Industrial welfare, HD7260-7780.8
Abstract: Abstract Background Perinatal exposure to titanium dioxide (TiO2), as a foodborne particle, may influence the intestinal barrier function and the susceptibility to develop inflammatory bowel diseases (IBD) later in life. Here, we investigate the impact of perinatal foodborne TiO2 exposure on the intestinal mucosal function and the susceptibility to develop IBD-associated colitis. Pregnant and lactating mother mice were exposed to TiO2 until pups weaning and the gut microbiota and intestinal barrier function of their offspring was assessed at day 30 post-birth (weaning) and at adult age (50 days). Epigenetic marks was studied by DNA methylation profile measuring the level of 5-methyl-2′-deoxycytosine (5-Me-dC) in DNA from colic epithelial cells. The susceptibility to develop IBD has been monitored using dextran-sulfate sodium (DSS)-induced colitis model. Germ-free mice were used to define whether microbial transfer influence the mucosal homeostasis and subsequent exacerbation of DSS-induced colitis. Results In pregnant and lactating mice, foodborne TiO2 was able to translocate across the host barriers including gut, placenta and mammary gland to reach embryos and pups, respectively. This passage modified the chemical element composition of foetus, and spleen and liver of mothers and their offspring. We showed that perinatal exposure to TiO2 early in life alters the gut microbiota composition, increases the intestinal epithelial permeability and enhances the colonic cytokines and myosin light chain kinase expression. Moreover, perinatal exposure to TiO2 also modifies the abilities of intestinal stem cells to survive, grow and generate a functional epithelium. Maternal TiO2 exposure increases the susceptibility of offspring mice to develop severe DSS-induced colitis later in life. Finally, transfer of TiO2-induced microbiota dysbiosis to pregnant germ-free mice affects the homeostasis of the intestinal mucosal barrier early in life and confers an increased susceptibility to develop colitis in adult offspring. Conclusions Our findings indicate that foodborne TiO2 consumption during the perinatal period has negative long-lasting consequences on the development of the intestinal mucosal barrier toward higher colitis susceptibility. This demonstrates to which extent environmental factors influence the microbial-host interplay and impact the long-term mucosal homeostasis.
Published: 2023
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6. Proenkephalin deletion in hematopoietic cells induces intestinal barrier failure resulting in clinical feature similarities with irritable bowel syndrome in mice

Author: Xavier Mas-Orea, Lea Rey, Louise Battut, Cyrielle Bories, Camille Petitfils, Anne Abot, Nadine Gheziel, Eve Wemelle, Catherine Blanpied, Jean-Paul Motta, Claude Knauf, Frederick Barreau, Eric Espinosa, Meryem Aloulou, Nicolas Cenac, Matteo Serino, Lionel Mouledous, Nicolas Fazilleau, and Gilles Dietrich
Subjects: Biology (General), QH301-705.5
Abstract: Abstract Opioid-dependent immune-mediated analgesic effects have been broadly reported upon inflammation. In preclinical mouse models of intestinal inflammatory diseases, the local release of enkephalins (endogenous opioids) by colitogenic T lymphocytes alleviate inflammation-induced pain by down-modulating gut-innervating nociceptor activation in periphery. In this study, we wondered whether this immune cell-derived enkephalin-mediated regulation of the nociceptor activity also operates under steady state conditions. Here, we show that chimeric mice engrafted with enkephalin-deficient bone marrow cells exhibit not only visceral hypersensitivity but also an increase in both epithelial paracellular and transcellular permeability, an alteration of the microbial topography resulting in increased bacteria-epithelium interactions and a higher frequency of IgA-producing plasma cells in Peyer’s patches. All these alterations of the intestinal homeostasis are associated with an anxiety-like behavior despite the absence of an overt inflammation as observed in patients with irritable bowel syndrome. Thus, our results show that immune cell-derived enkephalins play a pivotal role in maintaining gut homeostasis and normal behavior in mice. Because a defect in the mucosal opioid system remarkably mimics some major clinical symptoms of the irritable bowel syndrome, its identification might help to stratify subgroups of patients.
Published: 2023
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7. Development and Evaluation of a Hybrid Measurement System to Determine the Kinematics of the Wrist

Author: Jason Dellai, Martine A. Gilles, Olivier Remy, Laurent Claudon, and Gilles Dietrich
Subjects: MIMU, optical motion capture system, accuracy, wrist kinematic, hybrid system, Chemical technology, TP1-1185
Abstract: Optical Motion Capture Systems (OMCSs) are considered the gold standard for kinematic measurement of human movements. However, in situations such as measuring wrist kinematics during a hairdressing activity, markers can be obscured, resulting in a loss of data. Other measurement methods based on non-optical data can be considered, such as magneto-inertial measurement units (MIMUs). Their accuracy is generally lower than that of an OMCS. In this context, it may be worth considering a hybrid system [MIMU + OMCS] to take advantage of OMCS accuracy while limiting occultation problems. The aim of this work was (1) to propose a methodology for coupling a low-cost MIMU (BNO055) to an OMCS in order to evaluate wrist kinematics, and then (2) to evaluate the accuracy of this hybrid system [MIMU + OMCS] during a simple hairdressing gesture. During hair cutting gestures, the root mean square error compared with the OMCS was 4.53° (1.45°) for flexion/extension, 5.07° (1.30°) for adduction/abduction, and 3.65° (1.19°) for pronation/supination. During combing gestures, they were significantly higher, but remained below 10°. In conclusion, this system allows for maintaining wrist kinematics in case of the loss of hand markers while preserving an acceptable level of precision (
Published: 2024
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8. Tolerance of immersive head-mounted virtual reality among older nursing home residents

Author: Hajer Rmadi, Pauline Maillot, Romain Artico, Edouard Baudouin, Sylvain Hanneton, Gilles Dietrich, and Emmanuelle Duron
Subjects: older adults, virtual reality, tolerance, cybersickness, anxiety, Public aspects of medicine, RA1-1270
Abstract: IntroductionVirtual Reality (VR) is a tool that is increasingly used in the aging population. Head-Mounted Displays (HMDs) are stereoscopic vision devices used for immersive VR. Cybersickness is sometimes reported after head-mounted display (HMD) VR exposure. Cybersickness severity and anxiety state reflect VR low tolerance. We aimed to evaluate HMD VR tolerance among older nursing home residents through cybersickness and anxiety state.MethodsA total of 36 participants were included in this preliminary study, 33 of whom (mean age: 89.33 ± 5.48) underwent three individual HMD VR sessions with three different contents. Cybersickness occurrence and severity were scored by the Simulator Sickness Questionnaire (SSQ) after each session. Anxiety state was assessed by the State–Trait Anxiety Inventory form Y-A before and after each session. Anxiety trait (using State–Trait Anxiety Inventory form Y-B) was also evaluated before and after the experiment. In total, 92% (33/36) of patients completed all three sessions, of which 61% (20/33) did not report any cybersickness symptoms (SSQ = 0). Six participants reported significant cybersickness (defined by an SSQ score ⩾10) in at least one session.DiscussionOnly two participants stopped the study after the first exposure because of cybersickness. Age, cognitive function, anxiety trait, and well-being were not associated with cybersickness. The mean anxiety state decreased significantly from pre- to post-session. This immersive HMD VR experience was well tolerated among nursing home dwellers. Further larger studies in this population aiming to identify CS determinants are needed in order to use HMD VR on a standard basis.
Published: 2023
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9. Influence of Normal Aging and Multisensory Data Fusion on Cybersickness and Postural Adaptation in Immersive Virtual Reality

Author: Marie-Philippine Séba, Pauline Maillot, Sylvain Hanneton, and Gilles Dietrich
Subjects: Immersive Virtual Reality, age, cybersickness, postural control, Chemical technology, TP1-1185
Abstract: Immersive Virtual Reality (VR) systems are expanding as sensorimotor readaptation tools for older adults. However, this purpose may be challenged by cybersickness occurrences possibly caused by sensory conflicts. This study aims to analyze the effects of aging and multisensory data fusion processes in the brain on cybersickness and the adaptation of postural responses when exposed to immersive VR. Methods: We repeatedly exposed 75 participants, aged 21 to 86, to immersive VR while recording the trajectory of their Center of Pressure (CoP). Participants rated their cybersickness after the first and fifth exposure. Results: The repeated exposures increased cybersickness and allowed for a decrease in postural responses from the second repetition, i.e., increased stability. We did not find any significant correlation between biological age and cybersickness scores. On the contrary, even if some postural responses are age-dependent, a significant postural adaptation occurred independently of age. The CoP trajectory length in the anteroposterior axis and mean velocity were the postural parameters the most affected by age and repetition. Conclusions: This study suggests that cybersickness and postural adaptation to immersive VR are not age-dependent and that cybersickness is unrelated to a deficit in postural adaptation or age. Age does not seem to influence the properties of multisensory data fusion.
Published: 2023
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10. Delta opioid receptors on nociceptive sensory neurons mediate peripheral endogenous analgesia in colitis

Author: Xavier Mas-Orea, Lilian Basso, Catherine Blanpied, Claire Gaveriaux-Ruff, Nicolas Cenac, and Gilles Dietrich
Subjects: Visceral pain, Opioid receptors, Nociceptors, T lymphocytes, Opioids, Intestinal inflammation, Neurology. Diseases of the nervous system, RC346-429
Abstract: Abstract Background Inflammatory visceral pain is endogenously controlled by enkephalins locally released by mucosal CD4+ T lymphocytes in mice. The present study aimed at identifying opioid receptor(s) expressed on nociceptive sensory nerves involved in this peripheral opioid-mediated analgesia. Methods The peripheral analgesia associated with the accumulation of CD4+ T lymphocytes within the inflamed colonic mucosa was assessed in conditional knockout mice specifically deleted for either of the two opioid receptors for enkephalins (i.e., µ (MOR) and δ (DOR) receptors) in Nav1.8-expressing sensory neurons in the dextran sulfate sodium (DSS)-induced colitis model. Results Endogenous analgesia is lost in conditional knockout mice for DOR, but not MOR at the later phase of the DSS-induced colitis. The absence of either of the opioid receptors on sensory nerves had no impact on both the colitis severity and the rate of T lymphocytes infiltrating the inflamed colonic mucosa. Conclusion The key role of DOR on primary afferents in relieving intestinal inflammatory pain opens new therapeutic opportunities for peripherally restricted DOR analgesics to avoid most of the side effects associated with MOR-targeting drugs used in intestinal disorders.
Published: 2022
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11. Chemically diverse activity-based probes with unexpected inhibitory mechanisms targeting trypsin-like serine proteases

Author: Alba Ramos-Llorca, Lisse Decraecker, Valérie M. Y. Cacheux, Irena Zeiburlina, Michelle De bruyn, Louise Battut, Carlos Moreno-Cinos, Davide Ceradini, Eric Espinosa, Gilles Dietrich, Maya Berg, Ingrid De Meester, Pieter Van Der Veken, Guy Boeckxstaens, Anne-Marie Lambeir, Alexandre Denadai-Souza, and Koen Augustyns
Subjects: activity-based probe, serine protease, inhibitors, mast cells (MCs), irreversible inhibition, Chemistry, QD1-999
Abstract: Activity-based probes (ABP) are molecules that bind covalently to the active form of an enzyme family, making them an attractive tool for target and biomarker identification and drug discovery. The present study describes the synthesis and biochemical characterization of novel activity-based probes targeting trypsin-like serine proteases. We developed an extensive library of activity-based probes with “clickable” affinity tags and a diaryl phosphonate warhead. A wide diversity was achieved by including natural amino acid analogs as well as basic polar residues as side chains. A detailed enzymatic characterization was performed in a panel of trypsin-like serine proteases. Their inhibitory potencies and kinetic profile were examined, and their IC50 values, mechanism of inhibition, and kinetic constants were determined. The activity-based probes with a benzyl guanidine side chain showed the highest inhibitory effects in the panel. Surprisingly, some of the high-affinity probes presented a reversible inhibitory mechanism. On the other hand, probes with different side chains exhibited the expected irreversible mechanism. For the first time, we demonstrate that not only irreversible probes but also reversible probes can tightly label recombinant proteases and proteases released from human mast cells. Even under denaturing SDS-PAGE conditions, reversible slow-tight-binding probes can label proteases due to the formation of high-affinity complexes and slow dissociation rates. This unexpected finding will transform the view on the required irreversible nature of activity-based probes. The diversity of this library of activity-based probes combined with a detailed enzyme kinetic characterization will advance their applications in proteomic studies and drug discovery.
Published: 2023
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12. Mazor X Stealth versus O-arm navigation : a state-of-the-art technology for pedicle screw insertion and preliminary results of the first 100 patients

Author: Duccio Boscherini, Didier Grasset, Alain Akiki, Gilles Dietrich, Jonas Pierre Müller, and Marc Prod'homme
Subjects: Neurology. Diseases of the nervous system, RC346-429
Published: 2022
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13. Isolated Femoral LCL Avulsion Fracture in the Adult Knee: Two Patient Cases and Literature Review

Author: Gilles Dietrich, Benoît Maeder, John Nyland, Yaël Maeder, Alain Akiki, and Robin Martin
Subjects: Orthopedic surgery, RD701-811
Abstract: Avulsion injuries of the LCL most commonly occur at the fibular insertion. Femoral LCL avulsion injuries have only been previously described in pediatric patients or as multiligament knee injury components among adults. This case series with comprehensive literature review describes for the first time 2 cases of isolated LCL femoral avulsion fractures in adults including conservative treatment outcomes. Both patients sustained a strong varus stress mechanism to their right knee, following sport injury or road traffic accident. For both patients, a complete radiographic evaluation including X-rays, MRI, and CT scan confirmed no other associated knee lesions. The femoral LCL avulsion fractures that were observed were minimally displaced and noncomminuted. Furthermore, imagery suggested preserved integrity at the superior lateral genicular artery, adjacent articular capsule, and IT band. Based on clinical and imaging evaluations, the decision was made to follow conservative treatment. By 10 weeks postinjury, both patients were asymptomatic with early radiological fracture healing evidence. Comparative varus stress radiographs at 20° knee flexion revealed no side-to-side differences and clinical exam showed no posterolateral rotatory instability. The second patient case presented with mild femoral LCL attachment calcification on follow-up CT-scan. Following a detailed analysis of anatomic injury characteristics, we suggest that patients with isolated femoral LCL avulsion fractures have low secondary displacement risk provided SLGA, articular capsule, and IT band integrity are present. In contrast to high-grade ligamentous and distal avulsion LCL injuries, we recommend conservative treatment for patients who sustain these lesions.
Published: 2022
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14. Polyunsaturated fatty acid metabolites: biosynthesis in Leishmania and role in parasite/host interaction[S]

Author: Lucie Paloque, Teresa Perez-Berezo, Anne Abot, Jessica Dalloux-Chioccioli, Sandra Bourgeade-Delmas, Pauline Le Faouder, Julien Pujo, Marie-Ange Teste, Jean-Marie François, Nils Helge Schebb, Malwina Mainka, Corinne Rolland, Catherine Blanpied, Gilles Dietrich, Justine Bertrand-Michel, Céline Deraison, Alexis Valentin, and Nicolas Cenac
Subjects: cytochrome P450, infection, macrophages, ω-3, metabolism, arachidonic acid, Biochemistry, QD415-436
Abstract: Inside the human host, Leishmania infection starts with phagocytosis of infective promastigotes by macrophages. In order to survive, Leishmania has developed several strategies to manipulate macrophage functions. Among these strategies, Leishmania as a source of bioactive lipids has been poorly explored. Herein, we assessed the biosynthesis of polyunsaturated fatty acid metabolites by infective and noninfective stages of Leishmania and further explored the role of these metabolites in macrophage polarization. The concentration of docosahexaenoic acid metabolites, precursors of proresolving lipid mediators, was increased in the infective stage of the parasite compared with the noninfective stage, and cytochrome P450-like proteins were shown to be implicated in the biosynthesis of these metabolites. The treatment of macrophages with lipids extracted from the infective forms of the parasite led to M2 macrophage polarization and blocked the differentiation into the M1 phenotype induced by IFN-γ. In conclusion, Leishmania polyunsaturated fatty acid metabolites, produced by cytochrome P450-like protein activity, are implicated in parasite/host interactions by promoting the polarization of macrophages into a proresolving M2 phenotype.
Published: 2019
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15. Fluoro-registered Mazor X stealth edition versus O-arm navigation: Preliminary results of the first 21 patients

Author: Marc Prod'homme, Didier Grasset, Sébastien Lévy, Gilles Dietrich, Lionel Helfer, and Duccio Boscherini
Subjects: Neurology. Diseases of the nervous system, RC346-429
Published: 2021
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16. Identification of an analgesic lipopeptide produced by the probiotic Escherichia coli strain Nissle 1917

Author: Teresa Pérez-Berezo, Julien Pujo, Patricia Martin, Pauline Le Faouder, Jean-Marie Galano, Alexandre Guy, Claude Knauf, Jean Claude Tabet, Sophie Tronnet, Frederick Barreau, Maud Heuillet, Gilles Dietrich, Justine Bertrand-Michel, Thierry Durand, Eric Oswald, and Nicolas Cenac
Subjects: Science
Abstract: Escherichia coli Nissle is a probiotic that decreases visceral pain associated with irritable bowel syndrome. Here, the authors show that the microbe produces an analgesic lipopeptide, structurally related to GABA, that can cross the gut epithelial barrier and inhibits visceral hypersensitivity in mice.
Published: 2017
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17. Inflammation and Gut-Brain Axis During Type 2 Diabetes: Focus on the Crosstalk Between Intestinal Immune Cells and Enteric Nervous System

Author: Arnaud Bessac, Patrice D. Cani, Etienne Meunier, Gilles Dietrich, and Claude Knauf
Subjects: enteric nervous system, immune cells, microbiota, gut-brain axis, diabetes, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: The gut-brain axis is now considered as a major actor in the control of glycemia. Recent discoveries show that the enteric nervous system (ENS) informs the hypothalamus of the nutritional state in order to control glucose entry in tissues. During type 2 diabetes (T2D), this way of communication is completely disturbed leading to the establishment of hyperglycemia and insulin-resistance. Indeed, the ENS neurons are largely targeted by nutrients (e.g., lipids, peptides) but also by inflammatory factors from different origin (i.e., host cells and gut microbiota). Inflammation, and more particularly in the intestine, contributes to the development of numerous pathologies such as intestinal bowel diseases, Parkinson diseases and T2D. Therefore, targeting the couple ENS/inflammation could represent an attractive therapeutic solution to treat metabolic diseases. In this review, we focus on the role of the crosstalk between intestinal immune cells and ENS neurons in the control of glycemia. In addition, given the growing evidence showing the key role of the gut microbiota in physiology, we will also briefly discuss its potential contribution and role on the immune and neuronal systems.
Published: 2018
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18. Nod2: The intestinal gate keeper.

Author: Ziad Al Nabhani, Gilles Dietrich, Jean-Pierre Hugot, and Frederick Barreau
Subjects: Immunologic diseases. Allergy, RC581-607, Biology (General), QH301-705.5
Abstract: Nucleotide-binding oligomerization domain 2 (NOD2) is an intracellular pattern recognition receptor that senses bacterial peptidoglycan (PGN)-conserved motifs in cytosol and stimulates host immune response. The association of NOD2 mutations with a number of inflammatory pathologies, including Crohn disease (CD), Graft-versus-host disease (GVHD), and Blau syndrome, highlights its pivotal role in host-pathogen interactions and inflammatory response. Stimulation of NOD2 by its ligand (muramyl dipeptide) activates pro-inflammatory pathways such as nuclear factor-κB (NF-κB), mitogen-activated protein kinases (MAPKs), and Caspase-1. A loss of NOD2 function may result in a failure in the control of microbial infection, thereby initiating systemic responses and aberrant inflammation. Because the ligand of Nod2 is conserved in both gram-positive and gram-negative bacteria, NOD2 detects a wide variety of microorganisms. Furthermore, current literature evidences that NOD2 is also able to control viruses' and parasites' infections. In this review, we present and discuss recent developments about the role of NOD2 in shaping the gut commensal microbiota and pathogens, including bacteria, viruses, and parasites, and the mechanisms by which Nod2 mutations participate in disease occurrence.
Published: 2017
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19. Denatured G-protein coupled receptors as immunogens to generate highly specific antibodies.

Author: Franck Talmont, Lionel Moulédous, Jérôme Boué, Catherine Mollereau, and Gilles Dietrich
Subjects: Medicine, Science
Abstract: G-protein coupled receptors (GPCRs) play a major role in a number of physiological and pathological processes. Thus, GPCRs have become the most frequent targets for development of new therapeutic drugs. In this context, the availability of highly specific antibodies may be decisive to obtain reliable findings on localization, function and medical relevance of GPCRs. However, the rapid and easy generation of highly selective anti-GPCR antibodies is still a challenge. Herein, we report that highly specific antibodies suitable for detection of GPCRs in native and unfolded forms can be elicited by immunizing animals against purified full length denatured recombinant GPCRs. Contrasting with the currently admitted postulate, our study shows that an active and well-folded GPCR is not required for the production of specific anti-GPCR antibodies. This new immunizing strategy validated with three different human GPCR (μ-opioid, κ-opioid, neuropeptide FF2 receptors) might be generalized to other members of the GPCR family.
Published: 2012
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20. Théorie du corps lors de l’émersion de ses sensations internes : les dessins de conscience au Centre National des Arts du Cirque

Author: Gérard Fasoli, Gilles Dietrich, Raoul Bender, Cyril Thomas, Jonathan Collard, and Bernard Andrieu
Subjects: 03 medical and health sciences, Psychiatry and Mental health, 0302 clinical medicine, General Arts and Humanities, 030227 psychiatry
Abstract: Resume Objectif Il s’agit, a partir des dessins de conscience de ses sensations internes realises par les circassiens du Centre National des Arts du Cirque (CNAC) et de leurs verbatims, de decrire comment des sensations internes produites dans le corps vivant parviennent involontairement, par emersion, dans la conscience du corps vecu. Methodologie Nous utilisons une double methode : d’une part, faire dessiner ce que la conscience du circassien se represente du fonctionnement de ses sensations internes dans le cours d’une action corporelle ; d’autre part, leur faire dresser le recit temporel de cette action corporelle pour exprimer ce dessin de conscience et mettre en mots leur theorie du corps. Resultats Nous produisons ici plusieurs niveaux de dessins de conscience, accompagnes de leurs verbatims ecrits par les sujets correspondant a des elaborations differentes de theorie du corps : d’une part, la perception localisee des zones internes et externes de la peau definit une sensibilite chronique. D’autre part, la temporisation subjective des differents moments de la sensibilite corporelle demontre son ecart, le temps objectif du corps cerebrant le mouvement. Enfin, en ressentant l’espace arriere la representation mentale est rapportee aux coordonnees des sensations internes. Discussion La discussion porte essentiellement sur les modes de connaissance de cette clinique emersive de ses sensations internes. Face a la theorie de l’esprit, la theorie du corps, en s’appuyant sur les neurosciences in vivo, et ici les dessins de consciences et les verbatim en premiere personne, demontre que l’activation du corps vivant, dans les zones du cerveau et ses afferences sensorielles, est sensible par l’emersion par l’eveil d’une conscience qui prete attention a ce qui provient de l’interieur. Conclusion Cette theorie du corps, meme si elle ne correspond pas car invisible, au schema corporel incorpore et actif dans l’action constitue une croyance suffisamment vraisemblable pour le sujet pour qu’il reconnaissance, dessine et nomme ses sensations internes qui correspondraient a l’action interne de son corps vivant.
Published: 2022
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21. Conservative management of a specific subtype of Maisonneuve fractures: a report of two cases

Author: Gilles Dietrich, Marc Prod’homme, Jonas Müller, Tobias Ballhausen, and Lionel Helfer
Subjects: Case Report, General Medicine
Abstract: BACKGROUND: Maisonneuve fractures are most commonly characterised by a specific pattern with a medial malleolar fracture or deltoid ligament rupture, a disruption of the ankle syndesmosis ligaments and a fracture of the proximal fibula. CASE DESCRIPTION: We hereby describe for the first time two cases of conservative therapy of Maisonneuve fracture with intact medial structures and with associated posterior malleolus fracture. Patients were assessed with ankle radiographs and magnetic resonance imaging (MRI). The distal fibula was anatomically positioned in its notch and the deltoid ligament and interosseous membrane (IOM) were intact. In addition, the posterior malleolus fracture was not associated with talar subluxation or articular impaction, and the mortise remained anatomically positioned on the initial radiographs. Based on clinical and imaging evaluations, the decision was made to follow conservative treatment. Follow-up showed stability criteria on standing radiographs, and their evolution was clinically uneventful with a good AOFAS score after 1 year. CONCLUSIONS: The discussion emphasized the scarce description of conservative therapy of Maisonneuve fractures for which surgical treatment is considered to be the gold standard. The good results of these two cases are in favour with conservative therapy, avoiding adverse events and complications related to surgery, and showed that conservative therapy should be also considered as an effective therapeutic option in selected cases. We also emphasize that the results of our two cases are, moreover, in favor of an early weight-bearing protocol.
Published: 2022

22. Improving Movement Efficiency through Qualitative Slowness: A Discussion between Bergson’s Philosophy and Asian Martial Arts’ Pedagogy

Author: Alexandre Legendre and Gilles Dietrich
Subjects: Martial arts, Movement (music), 05 social sciences, Physical Therapy, Sports Therapy and Rehabilitation, 030229 sport sciences, 03 medical and health sciences, Philosophy, 0302 clinical medicine, Aesthetics, 0502 economics and business, Turning point, Sociology, Slowness, 050212 sport, leisure & tourism
Abstract: Bergson’s philosophy marked a turning point in Western understanding of time by differentiating quantitative time—apprehended by intelligence—from qualitative time—duration, embedded in consciousne...
Published: 2020
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23. Identification of bacterial lipopeptides as key players in IBS

Author: Camille Petitfils, Sarah Maurel, Gaelle Payros, Amandine Hueber, Bahija Agaiz, Géraldine Gazzo, Rémi Marrocco, Frédéric Auvray, Geoffrey Langevin, Jean-Paul Motta, Pauline Floch, Marie Tremblay-Franco, Jean-Marie Galano, Alexandre Guy, Thierry Durand, Simon Lachambre, Anaëlle Durbec, Hind Hussein, Lisse Decraecker, Justine Bertrand-Michel, Abdelhadi Saoudi, Eric Oswald, Pierrick Poisbeau, Gilles Dietrich, Chloe Melchior, Guy Boeckxstaens, Matteo Serino, Pauline Le Faouder, Nicolas Cenac, SEGUIN, Nathalie, APPEL À PROJETS GÉNÉRIQUE 2018 - Les lipopeptides produits par le microbiote : de l'hypersensibilité à la thérapie dans le syndrome de l'intestin irritable - - LiBacPain2018 - ANR-18-CE14-0039 - AAPG2018 - VALID, Signalisation des lipides du microbiote sur l'hôte - - MILI2020 - ANR-20-CE14-0011 - AAPG2020 - VALID, Ecole Universitaire de Recherche Interdisciplinaire sur la Douleur - - EURIDOL2017 - ANR-17-EURE-0022 - EURE - VALID, Développement d'une infrastructure française distribuée pour la métabolomique dédiée à l'innovation - - METABOHUB2011 - ANR-11-INBS-0010 - INBS - VALID, Equipements plateforme animalerie infectieuse de haute-sécurité de Midi Pyrénées - - ANINFIMIP2011 - ANR-11-EQPX-0003 - EQPX - VALID, Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), MetaToul Lipidomics, MetaboHUB-MetaToul, Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut des Maladies Métaboliques et Casdiovasculaires (UPS/Inserm U1297 - I2MC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des Maladies Métaboliques et Casdiovasculaires (UPS/Inserm U1297 - I2MC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des Neurosciences Cellulaires et Intégratives (INCI), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM), Université de Montpellier (UM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), ToxAlim (ToxAlim), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Metatoul AXIOM (E20 ), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-ToxAlim (ToxAlim), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), University of Gothenburg (GU), Nutrition, Inflammation et axe Microbiote-Intestin-Cerveau (ADEN), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-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), Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Centre d'Investigation Clinique [CHU Rouen] (CIC Rouen), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Normandie Université (NU)-Normandie Université (NU), Federation pour la Recherche sur le Cerveau (FRC) FRC20200411001, Centre National de la Recherche Scientifique. PP and GG received support from CNRS and University of Strasbourg. GG, CP and SM received a scholarship from Ministere de l'Enseignement Superieur, de la YRecherche et de l'Innovation., ANR-18-CE14-0039,LiBacPain,Les lipopeptides produits par le microbiote : de l'hypersensibilité à la thérapie dans le syndrome de l'intestin irritable(2018), ANR-20-CE14-0011,MILI,Signalisation des lipides du microbiote sur l'hôte(2020), ANR-17-EURE-0022,EURIDOL,Ecole Universitaire de Recherche Interdisciplinaire sur la Douleur(2017), ANR-11-INBS-0010,METABOHUB,Développement d'une infrastructure française distribuée pour la métabolomique dédiée à l'innovation(2011), and ANR-11-EQPX-0003,ANINFIMIP,Equipements plateforme animalerie infectieuse de haute-sécurité de Midi Pyrénées(2011)
Subjects: VISCERAL HYPERSENSITIVITY, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, IRRITABLE-BOWEL-SYNDROME, IRRITABLE BOWEL SYNDROME, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, ENTERIC BACTERIAL MICROFLORA, PRENATAL STRESS, INTESTINAL MICROBIOTA, LACTIC ACID BACTERIA, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.BC] Life Sciences [q-bio]/Cellular Biology, CLOSTRIDIUM-CLOSTRIDIOFORME, RISK, Science & Technology, Gastroenterology & Hepatology, Gastroenterology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, [SDV.BIO] Life Sciences [q-bio]/Biotechnology, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, SEVERITY, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Life Sciences & Biomedicine, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, LIPIDS
Abstract: ObjectivesClinical studies revealed that early-life adverse events contribute to the development of IBS in adulthood. The aim of our study was to investigate the relationship between prenatal stress (PS), gut microbiota and visceral hypersensitivity with a focus on bacterial lipopeptides containing γ-aminobutyric acid (GABA).DesignWe developed a model of PS in mice and evaluated, in adult offspring, visceral hypersensitivity to colorectal distension (CRD), colon inflammation, barrier function and gut microbiota taxonomy. We quantified the production of lipopeptides containing GABA by mass spectrometry in a specific strain of bacteria decreased in PS, in PS mouse colons, and in faeces of patients with IBS and healthy volunteers (HVs). Finally, we assessed their effect on PS-induced visceral hypersensitivity.ResultsPrenatally stressed mice of both sexes presented visceral hypersensitivity, no overt colon inflammation or barrier dysfunction but a gut microbiota dysbiosis. The dysbiosis was distinguished by a decreased abundance ofLigilactobacillus murinus, in both sexes, inversely correlated with visceral hypersensitivity to CRD in mice. An isolate from this bacterial species produced several lipopeptides containing GABA including C14AsnGABA. Interestingly, intracolonic treatment with C14AsnGABA decreased the visceral sensitivity of PS mice to CRD. The concentration of C16LeuGABA, a lipopeptide which inhibited sensory neurons activation, was decreased in faeces of patients with IBS compared with HVs.ConclusionPS impacts the gut microbiota composition and metabolic function in adulthood. The reduced capacity of the gut microbiota to produce GABA lipopeptides could be one of the mechanisms linking PS and visceral hypersensitivity in adulthood.
Published: 2022
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24. T helper cell-licensed mast cells promote inflammatory Th17 cells

Author: Gilles Dietrich, Edouard Leveque, Camille Petitfils, Salvatore Valitutti, Eric Espinosa, Xavier Mas-Orea, Camille Laurent, Nicolas Cenac, Régis Joulia, Gaëlle Payros, and Nicolas Gaudenzio
Subjects: Transcriptome, medicine.anatomical_structure, Immune system, Effector, Chemistry, Cell, medicine, Inflammation, T helper cell, medicine.symptom, Gene signature, Phenotype, Cell biology
Abstract: SummaryCD4+ T helper cells (Th) infiltrate sites of inflammation and orchestrate the immune response by instructing local leukocytes. Mast cells (MCs) are tissue sentinel cells particularly abundant in skin and mucosa. Here, we analyzed the interplay between human MCs and Th cells and, through the application of RNAseq and functional assays, showed that Th cells induced a specific transcriptomic program in helped MCs (named here MCTH) driving them toward an inflammatory phenotype. The gene signature of MCTH indicated that MCs helped by Th cell acquired in turn the capacity to regulate effector T cell response through wide-range of soluble and membrane ligands. Accordingly, we showed that MCTH promoted Th17 cells and notably an inflammatory subset of Th17, producing both IFN-γ and GM-CSF, through a PGE2 and IL-1β axis. Our findings demonstrate that activated effector/memory CD4+ T cells activate and instruct resting MCs toward a specific differentiated pro-inflammatory phenotype endowed with the capacity to speak back to effector T cells and to mold their functions.
Published: 2021
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25. Major acetabular prosthetic protrusion following total hip arthroplasty: a case report of a reconstruction challenge

Author: Marc Prod’homme, Gilles Dietrich, Lionel Helfer, Jonas Pierre Müller, Marc Barrera Uso, Didier Grasset, and Geoffroi Lallemand
Subjects: General Medicine
Published: 2022
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26. Colitis Linked to Endoplasmic Reticulum Stress Induces Trypsin Activity Affecting Epithelial Functions

Author: Delphine Bonnet, Nathalie Vergnolle, Sylvain Kirzin, Corinne Rolland, Muriel Quaranta-Nicaise, Alexandre Denadai-Souza, Anissa Edir, Laurent Alric, Nuria Sola Tapias, Emmanuel Mas, Gilles Dietrich, Marlène Marcellin, Frédérick Barreau, Carla Cirillo, Céline Deraison, Claire Rolland-Fourcade, Odile Burlet-Schiltz, Chrystelle Bonnart, Catherine Blanpied, Guillaume Portier, Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut de pharmacologie et de biologie structurale (IPBS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), CHU Toulouse [Toulouse], University of Calgary, ANR-11-JSV1-0001,IBD-ase,Identification des protéases impliquées dans les maladies inflammatoires chroniques de l'intestin et analyse moléculaire des conséquences de leur hyperactivité(2011), European Project: 310973,EC:FP7:ERC,ERC-2012-StG_20111109,PIPE(2013), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)
Subjects: 0301 basic medicine, Chemokine, Thapsigargin, Cell Culture Techniques, Inflammation, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Inflammatory bowel disease, Cell Line, 03 medical and health sciences, chemistry.chemical_compound, trypsin-like proteases, 0302 clinical medicine, Crohn Disease, medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Humans, Trypsin, Interleukin 8, sendoplasmic reticulum stress, Barrier function, biology, business.industry, Endoplasmic reticulum, Gastroenterology, intestinal epithelial cell, General Medicine, Endoplasmic Reticulum Stress, 3. Good health, Cell biology, Organoids, Enterocytes, 030104 developmental biology, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Intestinal Absorption, chemistry, Unfolded protein response, biology.protein, Colitis, Ulcerative, 030211 gastroenterology & hepatology, medicine.symptom, permeability, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, medicine.drug
Abstract: Background and Aims Intestinal epithelial cells [IECs] from inflammatory bowel disease [IBD] patients exhibit an excessive induction of endoplasmic reticulum stress [ER stress] linked to altered intestinal barrier function and inflammation. Colonic tissues and the luminal content of IBD patients are also characterized by increased serine protease activity. The possible link between ER stress and serine protease activity in colitis-associated epithelial dysfunctions is unknown. We aimed to study the association between ER stress and serine protease activity in enterocytes and its impact on intestinal functions Methods The impact of ER stress induced by Thapsigargin on serine protease secretion was studied using either human intestinal cell lines or organoids. Moreover, treating human intestinal cells with protease-activated receptor antagonists allowed us to investigate ER stress-resulting molecular mechanisms that induce proteolytic activity and alter intestinal epithelial cell biology. Results Colonic biopsies from IBD patients exhibited increased epithelial trypsin-like activity associated with elevated ER stress. Induction of ER stress in human intestinal epithelial cells displayed enhanced apical trypsin-like activity. ER stress-induced increased trypsin activity destabilized intestinal barrier function by increasing permeability and by controlling inflammatory mediators such as C-X-C chemokine ligand 8 [CXCL8]. The deleterious impact of ER stress-associated trypsin activity was specifically dependent on the activation of protease-activated receptors 2 and 4. Conclusions Excessive ER stress in IECs caused an increased release of trypsin activity that, in turn, altered intestinal barrier function, promoting the development of inflammatory process.
Published: 2021
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27. Bacteria-derived long chain fatty acid exhibits anti-inflammatory properties in colitis

Author: Gilles Dietrich, Catherine Blanpied, Filip Van Immerseel, Claude Knauf, Pauline Le Faouder, Julien Pujo, Camille Petitfils, Sarah Maurel, Gaelle Payros, Teresa Pérez-Berezo, Stéphane Chavanas, Patrice D. Cani, Matthias Van Hul, Venessa Eeckhaut, Justine Bertrand-Michel, Eric Oswald, Frédérick Barreau, Nicolas Cenac, Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), McMaster University [Hamilton, Ontario], Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Universiteit Gent = Ghent University [Belgium] (UGENT), Université Catholique de Louvain = Catholic University of Louvain (UCL), Centre de Physiopathologie Toulouse Purpan (CPTP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), FNRS : WELBIO-CR-2019C-02R, FNRS : 'The Excellence Of Science: EOS 30770923', Funds Baillet Latour (Grant for Medical Research 2015), ANR-18-CE14-0039,LiBacPain,Les lipopeptides produits par le microbiote : de l'hypersensibilité à la thérapie dans le syndrome de l'intestin irritable(2018), ANR-18-CE14-0007,ENDIABAC,LE SYSTEME NERVEUX ENTERIQUE COMME CIBLE POUR TRAITER LE DIABETE DE TYPE 2 : ROLES DES LIPIDES BIOACTIFS BACTERIENS(2018), and UCL - SSS/LDRI - Louvain Drug Research Institute
Subjects: Cell Membrane Permeability, Chemokine CXCL1, medicine.medical_treatment, Interleukin-1beta, Gene Expression, Oligosaccharides, Peroxisome proliferator-activated receptor, Pancreatitis-Associated Proteins, Gut flora, medicine.disease_cause, Mass Spectrometry, law.invention, Mice, Peyer's Patches, Probiotic, 0302 clinical medicine, law, Intestinal Mucosa, chemistry.chemical_classification, 0303 health sciences, biology, Dextran Sulfate, Gastroenterology, Colitis, Lipids, Enteric bacterial microflora, Experimental colitis, 3. Good health, enteric bacterial microflora, 030211 gastroenterology & hepatology, lipids (amino acids, peptides, and proteins), Long chain fatty acid, experimental colitis, Firmicutes, Permeability, Microbiology, lipids, 03 medical and health sciences, Stearates, Escherichia coli, medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Animals, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, Bacteroidetes, Probiotics, Prebiotic, Epithelial Cells, medicine.disease, biology.organism_classification, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Gastrointestinal Microbiome, PPAR gamma, Prebiotics, chemistry, probiotics, Zonula Occludens-1 Protein, Caco-2 Cells, Bacteria, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: ObjectiveData from clinical research suggest that certain probiotic bacterial strains have the potential to modulate colonic inflammation. Nonetheless, these data differ between studies due to the probiotic bacterial strains used and the poor knowledge of their mechanisms of action.DesignBy mass-spectrometry, we identified and quantified free long chain fatty acids (LCFAs) in probiotics and assessed the effect of one of them in mouse colitis.ResultsAmong all the LCFAs quantified by mass spectrometry in Escherichia coli Nissle 1917 (EcN), a probiotic used for the treatment of multiple intestinal disorders, the concentration of 3-hydroxyoctadecaenoic acid (C18-3OH) was increased in EcN compared with other E. coli strains tested. Oral administration of C18-3OH decreased colitis induced by dextran sulfate sodium in mice. To determine whether other bacteria composing the microbiota are able to produce C18-3OH, we targeted the gut microbiota of mice with prebiotic fructooligosaccharides (FOS). The anti-inflammatory properties of FOS were associated with an increase in colonic C18-3OH concentration. Microbiota analyses revealed that the concentration of C18-3OH was correlated with an increase in the abundance in Allobaculum, Holdemanella and Parabacteroides. In culture, Holdemanella biformis produced high concentration of C18-3OH. Finally, using TR-FRET binding assay and gene expression analysis, we demonstrated that the C18-3OH is an agonist of peroxisome proliferator activated receptor gamma.ConclusionThe production of C18-3OH by bacteria could be one of the mechanisms implicated in the anti-inflammatory properties of probiotics. The production of LCFA-3OH by bacteria could be implicated in the microbiota/host interactions.
Published: 2021
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28. Analgesic Effects of Topical Amitriptyline in Patients With Chemotherapy-Induced Peripheral Neuropathy: Mechanistic Insights From Studies in Mice

Author: Paola Principe, Virginie Penalba, Myriam Ducrocq, Séverine Hatton, Patrick Delmas, Jérôme Ruel, Camille Petitfils, Gilles Dietrich, Céline Greco, Anne-Laure Genevois, Département de Pathologie [CHU Necker], Université Sorbonne Paris Cité (USPC)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPC), Laboratoire de Neurosciences Cognitives [Marseille] (LNC), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), AlgoTherapeutix, Modèles de Cellules Souches Malignes et Thérapeutiques, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Sante Active Edition, Ecole de l’Inserm Liliane-Bettencourt, Fondation Bettencourt-Schueller, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), and Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: Male, Administration, Topical, Pharmacology, Nociceptive Pain, Mice, 0302 clinical medicine, 030202 anesthesiology, voltage-gated sodium channels, Amitriptyline, Child, TRPA1 Cation Channel, Aged, 80 and over, Voltage-Gated Sodium Channel Blockers, Behavior, Animal, NAV1.7 Voltage-Gated Sodium Channel, Chronic pain, Peripheral Nervous System Diseases, Analgesics, Non-Narcotic, Middle Aged, 3. Good health, Neurology, Chemotherapy-induced peripheral neuropathy, Neuropathic pain, Nociceptor, analgesics, Female, medicine.drug, chemotherapy-induced peripheral neuropathy, Adult, Adolescent, Amitriptyline Hydrochloride, Analgesic, Antineoplastic Agents, NAV1.8 Voltage-Gated Sodium Channel, Young Adult, 03 medical and health sciences, [SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication, medicine, Animals, Humans, [SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs, NAV1.9 Voltage-Gated Sodium Channel, Aged, business.industry, nociceptive sensory neurons, medicine.disease, Mice, Inbred C57BL, Disease Models, Animal, Anesthesiology and Pain Medicine, Peripheral neuropathy, nociceptors, topical adminis-tration, Neurology (clinical), transient receptor potentialankyrin 1, business, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Oral amitriptyline hydrochloride (amitriptyline) is ineffective against some forms of chronic pain and is often associated with dose-limiting adverse events. We evaluated the potential effectiveness of high-dose topical amitriptyline in a preliminary case series of chemotherapy-induced peripheral neuropathy patients and investigated whether local or systemic adverse events associated with the use of amitriptyline were present in these patients. We also investigated the mechanism of action of topically administered amitriptyline in mice. Our case series suggested that topical 10% amitriptyline treatment was associated with pain relief in chemotherapy-induced peripheral neuropathy patients, without the side effects associated with systemic absorption. Topical amitriptyline significantly increased mechanical withdrawal thresholds when applied to the hind paw of mice, and inhibited the firing responses of C-, Aβ- and Aδ-type peripheral nerve fibers in ex vivo skin-saphenous nerve preparations. Whole-cell patch-clamp recordings on cultured sensory neurons revealed that amitriptyline was a potent inhibitor of the main voltage-gated sodium channels (Nav1.7, Nav1.8, and Nav1.9) found in nociceptors. Calcium imaging showed that amitriptyline activated the transient receptor potential cation channel, TRPA1. Our case series indicated that high-dose 10% topical amitriptyline could alleviate neuropathic pain without adverse local or systemic effects. This analgesic action appeared to be mediated through local inhibition of voltage-gated sodium channels. Perspective: Our preliminary case series suggested that topical amitriptyline could provide effective pain relief for chemotherapy-induced peripheral neuropathy patients without any systemic or local adverse events. Investigation of the mechanism of this analgesic action in mice revealed that this activity was mediated through local inhibition of nociceptor Nav channels.
Published: 2021
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29. Pain Management in a Model of Interstitial Cystitis/Bladder Pain Syndrome by a Vaccinal Strategy

Author: Sophie Chabot, Céline Augé, Catherine Blanpied, Nathalie Vergnolle, Philippe Lluel, Gilles Dietrich, Lilian Basso, and Xavier Gamé
Subjects: 0301 basic medicine, medicine.medical_specialty, Cyclophosphamide, business.industry, Analgesic, Urology, Interstitial cystitis, Visceral pain, Chronic Cystitis, medicine.disease, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Nociception, Opioid, medicine, medicine.symptom, Bladder Pain, business, 030217 neurology & neurosurgery, medicine.drug
Abstract: Current analgesic treatments for Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS) are limited. Here, we propose a novel antinociceptive strategy exploiting the opioid-mediated analgesic properties of T lymphocytes to relieve from bladder pain. In a chronic model of IC/BPS in rats, we show that a secondary T cell response against intravesically administered ovalbumin prevents from visceral pain in OVA-primed animals. The analgesic effect is associated with the recruitment of T lymphocytes within the inflamed mucosa and is reversed by naloxone-methiodide, a peripheral opioid receptor antagonist. Similarly, intravesical instillation of BCG or tetanus toxoid antigens in vaccinated rats protects from pain in the same model. We show opioid-dependent analgesic properties of local vaccine antigen recall in a preclinical rat model of chronic cystitis. Since BCG bladder instillation is regularly used in humans (as anticancer therapy), our results open it as a new therapeutic positioning for a pain management indication for IC/BPS patients.
Published: 2020

30. Endothelin-1 Exhibiting Pro-Nociceptive and Pro-Peristaltic Activities Is Increased in Peritoneal Carcinomatosis

Author: Leila Lafendi, Cleo Desormeaux, Antoinette Lemoine, Ying-Ying Zhu, Benedicte Demuynck, Nicolas Cenac, Lilian Basso, Gilles Dietrich, Sylvie Chapiro, Céline Greco, Audren Fournel, Claude Knauf, and Claude Boucheix
Subjects: medicine.medical_specialty, Abdominal pain, business.industry, Visceral pain, medicine.disease, Endothelin 1, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Nociception, Mechanism of action, 030220 oncology & carcinogenesis, Internal medicine, medicine, General Earth and Planetary Sciences, 030211 gastroenterology & hepatology, medicine.symptom, Ovarian cancer, Endothelin receptor, Receptor, business, General Environmental Science
Abstract: Background: Peritoneal carcinomatosis often results in alterations in intestinal peristalsis and recurrent abdominal pain. Pain management in these patients is often unsatisfactory. This study aimed to investigate whether endothelin-1 (EDN1) was involved in pain mediation in peritoneal carcinomatosis, and thus whether the EDN1 pathway could be a new therapeutic target for peritoneal carcinomatosis-associated pain.Methods: EDN1 plasma levels and abdominal pain severity were assessed in patients with abdominal tumors, with or without peritoneal carcinomatosis, and in healthy donors. The effects of EDN1 on the visceromotor response to colorectal distension, and on colonic contractions were then examined in mice, and the mechanism of action of EDN1 was then investigated by measuring the impact of EDN1 exposure on calcium mobilization in cultured neurons. Inhibition studies were also performed to determine if the effects of EDN1 exposure could be reversed by EDN1-specific receptor antagonists.Results: A positive correlation between EDN1 plasma levels and abdominal pain was identified in patients with peritoneal carcinomatosis. EDN1 exposure increased visceral sensitivity and the amplitude of colonic contractions in mice and induced calcium mobilization by direct binding to its receptors on sensory neurons. The effects of EDN1 were inhibited by antagonists of the EDN1 receptors.Conclusions: This preliminary study, using data from patients with peritoneal carcinomatosis combined with data from experiments performed in mice, suggests that EDN1 may play a key role mediating pain in peritoneal carcinomatosis. Our findings suggest that antagonists of the EDN1 receptors might be beneficial in the management of pain in patients with peritoneal carcinomatosis.
Published: 2020

31. Pharmacological insight into the activation of the human Neuropeptide FF2 receptor

Author: Catherine Mollereau, Franck Talmont, Remi Veneziano, Jean-Marie Zajac, Lionel Moulédous, Gilles Dietrich, Institut de pharmacologie et de biologie structurale (IPBS), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées
Subjects: Receptors, Neuropeptide, Physiology, G protein, Neuropeptide, 030209 endocrinology & metabolism, Biochemistry, Adenylyl cyclase, 03 medical and health sciences, Cellular and Molecular Neuroscience, chemistry.chemical_compound, Structure-Activity Relationship, 0302 clinical medicine, Endocrinology, Cricetinae, Aspartic acid, Animals, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Amino Acid Sequence, Receptor, Cells, Cultured, ComputingMilieux_MISCELLANEOUS, G protein-coupled receptor, C-terminus, Neuropeptides, Cell biology, Analgesics, Opioid, chemistry, Mutagenesis, Signal transduction, 030217 neurology & neurosurgery, Signal Transduction
Abstract: International audience; The neuropeptide FF2 (NPFF 2) receptor, predominantly expressed in the central nervous system, plays an important role in the modulation of sensory input and opioid analgesia, as well as in locomotion, feeding, intestinal motility, reward, and the control of obesity. The NPFF 2 receptor belongs to the RFamide peptide receptor family and to the G protein coupled receptor (GPCR) super family, but contrary to many other class A GPCRs, no 3D structure has been solved. Thus, it is essential to perform mutagenesis to gain information on the fine functioning of the NPFF 2 receptor. In this study, we examined the role of aspartic acid (D) from the "D/ERY/F" motif found in the second intracellular loop (ICL2) and the role of the C-terminal end of the receptor in ligand binding and signal transduction. We found that mutation D3.49A does not impair binding capacities but inhibits G protein activation as well as adenylyl cyclase regulation. Truncation of the C terminal part of the receptor has different effects depending on the position of truncation. When truncation was realized downstream of the putative acylation site, ligand binding and signal transduction capabilities were not lost, contrary to total deletion of the C terminus, which totally impairs the activity of the receptor.
Published: 2020
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32. Identification of new enterosynes using prebiotics: roles of bioactive lipids and mu-opioid receptor signalling in humans and mice

Author: Giulio G. Muccioli, Adrien Paquot, Claire Laurens, Alexandre Lucas, Amandine Everard, Etienne Meunier, Cedric Moro, Christophe Fremez, Patrice D. Cani, Arnaud Bessac, Nicolas Pomie, Deborah Carper, Claude Knauf, Jean Lesage, Maxime Fontanie, Eve Wemelle, Xavier Mas Orea, Anne Abot, Gilles Dietrich, Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Enterosys, NeuroMicrobiota, Université Catholique de Louvain = Catholic University of Louvain (UCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS), Centre National d’Études Spatiales [Paris] (CNES), Université de Strasbourg (UNISTRA), Université Catholique de Louvain = Catholic University of Louvain (UCL), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de pharmacologie et de biologie structurale (IPBS), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Université de Lille - Faculté des Humanités (Lille Humanités), Université de Lille, FRS-FNRS (Fonds de la Recherche Scientifique), UCL - SSS/LDRI - Louvain Drug Research Institute, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), European Associated Laboratory NeuroMicrobiota (INSERM/UCL), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université de Lille - UFR des Humanités (Lille UFRH), SEGUIN, Nathalie, and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Blood Glucose, Male, Enkephalin, [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], medicine.medical_treatment, Receptors, Opioid, mu, Oligosaccharides, Nitric Oxide Synthase Type I, Pharmacology, Gut flora, Enteric Nervous System, Mice, 0302 clinical medicine, enteric nervous system, Brain-Gut Axis, 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid, Gut Microbiota, Receptor, Neurons, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Gastroenterology, Enkephalins, Middle Aged, Hedgehog signaling pathway, 3. Good health, Proenkephalin, diabetes mellitus, prebiotic, motility disorders, μ-opioid receptor, Signal Transduction, Adult, Duodenum, 030209 endocrinology & metabolism, Biology, Diabetes Mellitus, Experimental, lipids, 03 medical and health sciences, medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Animals, Humans, Isotonic Contraction, RNA, Messenger, Protein Precursors, Aged, Prebiotic, Muscle, Smooth, Glucose Tolerance Test, biology.organism_classification, Gastrointestinal Microbiome, PPAR gamma, 030104 developmental biology, Prebiotics, Diabetes Mellitus, Type 2, Enteric nervous system, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: ObjectiveThe enteric nervous system (ENS) plays a key role in controlling the gut-brain axis under normal and pathological conditions, such as type 2 diabetes. The discovery of intestinal actors, such as enterosynes, able to modulate the ENS-induced duodenal contraction is considered an innovative approach. Among all the intestinal factors, the understanding of the role of gut microbes in controlling glycaemia is still developed. We studied whether the modulation of gut microbiota by prebiotics could permit the identification of novel enterosynes.DesignWe measured the effects of prebiotics on the production of bioactive lipids in the intestine and tested the identified lipid on ENS-induced contraction and glucose metabolism. Then, we studied the signalling pathways involved and compared the results obtained in mice to human.ResultsWe found that modulating the gut microbiota with prebiotics modifies the actions of enteric neurons, thereby controlling duodenal contraction and subsequently attenuating hyperglycaemia in diabetic mice. We discovered that the signalling pathway involved in these effects depends on the synthesis of a bioactive lipid 12-hydroxyeicosatetraenoic acid (12-HETE) and the presence of mu-opioid receptors (MOR) on enteric neurons. Using pharmacological approaches, we demonstrated the key role of the MOR receptors and proliferator-activated receptor γ for the effects of 12-HETE. These findings are supported by human data showing a decreased expression of the proenkephalin and MOR messanger RNAs in the duodenum of patients with diabetic.ConclusionsUsing a prebiotic approach, we identified enkephalin and 12-HETE as new enterosynes with potential real beneficial and safety impact in diabetic human.
Published: 2020
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33. Skier-ski system model and development of a computer simulation aiming to improve skier's performance and ski.

Author: François Roux, Gilles Dietrich, and Aude-Clémence Doix
Published: 2010
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34. Mobilization of CD4+ T lymphocytes in inflamed mucosa reduces pain in colitis mice: toward a vaccinal strategy to alleviate inflammatory visceral pain

Author: Lilian Basso, Nathalie Vergnolle, Jérôme Boué, Catherine Blanpied, Céline Deraison, Céline Augé, Gilles Dietrich, Philippe Lluel, and Nicolas Cenac
Subjects: CD4-Positive T-Lymphocytes, Male, 0301 basic medicine, Abdominal pain, Ovalbumin, Freund's Adjuvant, Analgesic, Mice, Transgenic, Statistics, Nonparametric, Mice, 03 medical and health sciences, 0302 clinical medicine, Antigen, medicine, Animals, Protein Precursors, Colitis, Bovine serum albumin, Mucous Membrane, biology, CD11 Antigens, business.industry, Visceral pain, Enkephalins, Visceral Pain, medicine.disease, Acquired immune system, 3. Good health, Mice, Inbred C57BL, Disease Models, Animal, 030104 developmental biology, Anesthesiology and Pain Medicine, Neurology, Immunology, biology.protein, Immunization, Neurology (clinical), medicine.symptom, business, 030217 neurology & neurosurgery
Abstract: T lymphocytes play a pivotal role in endogenous regulation of inflammatory visceral pain. The analgesic activity of T lymphocytes is dependent on their production of opioids, a property acquired on antigen activation. Accordingly, we investigated whether an active recruitment of T lymphocytes within inflamed colon mucosa via a local vaccinal strategy may counteract inflammation-induced visceral pain in mice. Mice were immunized against ovalbumin (OVA). One month after immunization, colitis was induced by adding 3% (wt/vol) dextran sulfate sodium into drinking water containing either cognate antigen OVA or control antigen bovine serum albumin for 5 days. Noncolitis OVA-primed mice were used as controls. Visceral sensitivity was then determined by colorectal distension. Oral administration of OVA but not bovine serum albumin significantly reduced dextran sulfate sodium-induced abdominal pain without increasing colitis severity in OVA-primed mice. Analgesia was dependent on local release of enkephalins by effector anti-OVA T lymphocytes infiltrating the inflamed mucosa. The experiments were reproduced with the bacillus Calmette-Guerin vaccine as antigen. Similarly, inflammatory visceral pain was dramatically alleviated in mice vaccinated against bacillus Calmette-Guerin and then locally administered with live Mycobacterium bovis. Together, these results show that the induction of a secondary adaptive immune response against vaccine antigens in inflamed mucosa may constitute a safe noninvasive strategy to relieve from visceral inflammatory pain.
Published: 2017
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35. Robotic-assisted gait training improves walking abilities in diplegic children with cerebral palsy

Author: Laura Wallard, Y. Kerlirzin, J. Bredin, and Gilles Dietrich
Subjects: Male, 030506 rehabilitation, medicine.medical_specialty, Population, Walking, Kinematics, Cerebral palsy, 03 medical and health sciences, 0302 clinical medicine, Gait (human), Physical medicine and rehabilitation, Gait training, medicine, Spastic, Humans, Child, education, Gait, Postural Balance, Balance (ability), education.field_of_study, Cerebral Palsy, Robotics, General Medicine, medicine.disease, Sagittal plane, Biomechanical Phenomena, Exercise Therapy, medicine.anatomical_structure, Pediatrics, Perinatology and Child Health, Physical therapy, Female, Neurology (clinical), 0305 other medical science, Psychology, 030217 neurology & neurosurgery
Abstract: The robotic-assisted gait training therapy (RAGT), based on intensity and repetition of movement, presents beneficial effects on recovery and improvement of postural and locomotor functions of the patient. This study sought to highlight the effect of this RAGT on the dynamic equilibrium control during walking in children with Cerebral Palsy (CP) by analyzing the different postural strategies of the fullbody (upper/lower body) before and after this RAGT in order to generate forward motion while maintaining balance. Data were collected by a motion analysis system (Vicon® - Oxford Metrics). Thirty children with bilateral spastic CP were evaluated using a full-body marker set which allows assessing both the lower and upper limb kinematics. The children were divided into two groups in such a way as to obtain a randomized controlled population: i) a group of fourteen children (Treated Group) underwent 20 sessions of RAGT using the driven gait orthosis Lokomat®Pediatric (Hocoma) compared to ii) a group of sixteen children without sessions of Lokomat®Pediatric (Control Group) receiving only daily physiotherapy. Significant improvements are observed between the TG pre- and post-test values of i) the kinematic data of the full-body in the sagittal and frontal planes and ii) the Gross Motor Function Measure test (D and E). This study shows the usefulness of this RAGT mainly in the balance control in gait. Indeed, the Treated Group use new dynamic strategies of gait that are especially characterized by a more appropriate control of the upper body associated with an improvement of the lower limbs kinematics.
Published: 2017
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36. T-lymphocyte-derived enkephalins reduce Th1/Th17 colitis and associated pain in mice

Author: Nicolas Cenac, Jérôme Boué, Sophie Laffont, Arnaud Bessac, Gilles Dietrich, Laure Garnier, Lilian Basso, Catherine Blanpied, Institut de Recherche en Santé Digestive (IRSD ), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Physiopathologie Toulouse Purpan ex IFR 30 et IFR 150 (CPTP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT)
Subjects: 0301 basic medicine, enkephalin, Enkephalin, medicine.drug_class, T lymphocytes, Intestinal inflammation, Inflammation, enképhaline, (+)-Naloxone, lymphocyte, 03 medical and health sciences, 0302 clinical medicine, Opioid receptor, inflammation intestinale, Medicine, pain, Colitis, T-lymphocytes, Endogenous opioid, business.industry, Gastroenterology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Visceral pain, Enkephalins, medicine.disease, 3. Good health, 030104 developmental biology, Opioid, Immunology, douleur, medicine.symptom, business, 030217 neurology & neurosurgery, medicine.drug
Abstract: BACKGROUND:Endogenous opioids, including enkephalins, are fundamental regulators of pain. In inflammatory conditions, the local release of opioids by leukocytes at the inflammatory site inhibits nociceptor firing, thereby inducing analgesia. Accordingly, in chronic intestinal Th1/Th17-associated inflammation, enkephalins released by colitogenic CD4+ T lymphocytes relieve inflammation-induced visceral pain. The present study aims to investigate whether mucosal T-cell-derived enkephalins also exhibit a potent anti-inflammatory activity as described for exogenous opioid drugs in Th1/Th17-associated colitis.METHODS:The anti-inflammatory effects of endogenous opioids were investigated in both Th1/Th17-associated (transfer of CD4+CD45RBhigh T lymphocytes) and Th2-associated (oxazolone) colitis models in mice. Inflammation-induced colonic damage and CD4+ T cell subsets were compared in mice treated or not treated with naloxone methiodide, a peripheral antagonist of opioid receptors. The anti-inflammatory activity of T-cell-derived enkephalins was further estimated by comparison of colitis severity in immunodeficient mice into which naïve CD4+CD45RBhigh T lymphocytes originating from wild-type or enkephalin-knockout mice had been transferred.RESULTS:Peripheral opioid receptor blockade increases the severity of Th1/Th17-induced colitis and attenuates Th2 oxazolone colitis. The opposite effects of naloxone methiodide treatment in these two models of intestinal inflammation are dependent on the potency of endogenous opioids to promote a Th2-type immune response. Accordingly, the transfer of enkephalin-deficient CD4+CD45RBhigh T lymphocytes into immunodeficient mice exacerbates inflammation-induced colonic injury.CONCLUSIONS:Endogenous opioids, including T-cell-derived enkephalins, promote a Th2-type immune response, which, depending on the context, may either attenuate (Th1/Th17-associated) or aggravate (Th2-associated) intestinal inflammation.
Published: 2017
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37. Swiss Mountain Guides: Medical Education, Knowledge, and Practice

Author: Urs Wiget, Claudio Sartori, Jacques Richon, Pierre Métrailler, Gilles Dietrich, Daniel Walter, Jens Greiser, and Martin Walliser
Subjects: Male, Medical knowledge, Health Knowledge, Attitudes, Practice, Physiology, Hypertension, Pulmonary, Wilderness Medicine, Brain Edema, 030204 cardiovascular system & hematology, Altitude Sickness, Objective assessment, 03 medical and health sciences, 0302 clinical medicine, Education, Professional, Surveys and Questionnaires, medicine, Humans, Curriculum, Emergency Treatment, Objective knowledge, Medical education, business.industry, Altitude, Public Health, Environmental and Occupational Health, 030229 sport sciences, General Medicine, Middle Aged, medicine.disease, Mountaineering, Female, business, High-altitude cerebral edema, Switzerland, First aid
Abstract: Background: Mountain guides work daily in remote areas and high-altitude locations where specific hypoxia-related and common medical problems may occur. Arrival of rescue teams can be delayed, so mountain guides often have to rely on their own capabilities to provide first aid. Therefore, IFMGA-recognized Swiss mountain guides receive a specific medical education and are equipped with a dedicated medical kit. This specific education has never been evaluated. Methods: A questionnaire was sent to all Swiss mountain guides through their national association. This questionnaire evaluates guides' activity, type, and frequency of medical events encountered, medical education, and use of the medical kit. Furthermore, clinical vignettes were used to evaluate their subjective and objective knowledge about prevention and treatment of specific altitude-related diseases. Results: A total of 467 guides completed the questionnaire, 54 (11.6%) of them were identified as high-altitude guides (HA-guides), because they spent ≥10 nights above 4000 meters each year. Mountain guides are more exposed to altitude-specific pathologies, such as Acute Mountain Sickness (AMS), High-Altitude Pulmonary Edema (HAPE), and High-Altitude Cerebral Edema (HACE) than to general medical conditions. A majority of participants (in particular HA-guides) considered altitude-related medical knowledge essential but judged their own education as insufficient. A majority of mountain guides were aware of nonpharmacological preventive measures and able to recognize altitude-related diseases. Mountain guides declared themselves as very confident in treating altitude-related diseases. Objective assessment of their knowledge showed some gaps, in particular related to the use of specific medications like nifedipine and dexamethasone. Conclusions: Swiss mountain guides' education in altitude medicine may be improved, in particular concerning the recognition and treatment of severe conditions such as HAPE and HACE. Better knowledge may be especially important for HA-guides. These data have induced experts in the field to adapt the guides teaching curriculum and medical kit.
Published: 2019

38. Polyunsaturated fatty acid metabolites: biosynthesis in Leishmania and role in parasite/host interaction

Author: Julien Pujo, Jean Marie François, Jessica Dalloux-Chioccioli, Pauline Le Faouder, Anne Abot, Lucie Paloque, Teresa Pérez-Berezo, Marie-Ange Teste, Gilles Dietrich, Malwina Mainka, Alexis Valentin, Nicolas Cenac, Justine Bertrand-Michel, Sandra Bourgeade-Delmas, Nils Helge Schebb, Céline Deraison, Corinne Rolland, Catherine Blanpied, Laboratoire de chimie de coordination (LCC), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Ingénierie des Systèmes Biologiques et des Procédés (LISBP), Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Recherche Agronomique (INRA), Faculty of Mathematics and Natural Sciences, Institut de Chimie de Toulouse (ICT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Université de Toulouse (UT), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), MetaToul Lipidomics, Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-MetaboHUB-MetaToul, MetaboHUB-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-MetaboHUB-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut National de la Recherche Agronomique (INRA)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), University of Wuppertal, Region Midi-Pyrenees, ANR-11-INBS-0010,METABOHUB,Développement d'une infrastructure française distribuée pour la métabolomique dédiée à l'innovation(2011), European Project: 627487,EC:FP7:PEOPLE,FP7-PEOPLE-2013-IOF,EPIMACASE(2014), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Institut de Recherche pour le Développement (IRD), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Plateau MetaToul-LIPIDOMIQUE = MetaToul-Lipidomics, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-MetaToul-MetaboHUB, Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Gulli, Marie-Hélène, Développement d'une infrastructure française distribuée pour la métabolomique dédiée à l'innovation - - METABOHUB2011 - ANR-11-INBS-0010 - INBS - VALID, THE ROLE OF ELASTASE/ELASTASE INHIBITOR IN DIALOG BETWEEN INTESTINAL EPITHELIAL CELLS AND MACROPHAGES IN INFLAMMATORY BOWEL DISEASES CONTEXT - EPIMACASE - - EC:FP7:PEOPLE2014-08-06 - 2016-08-05 - 627487 - VALID, Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-MetaboHUB-MetaToul, Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole Nationale Vétérinaire de Toulouse (ENVT), and Institut National des Sciences Appliquées (INSA)-Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées (INSA)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, 0301 basic medicine, Cytochrome P450, 030204 cardiovascular system & hematology, Biochemistry, Mice, chemistry.chemical_compound, 0302 clinical medicine, Endocrinology, Macrophage, Research Articles, Leishmania, chemistry.chemical_classification, biology, Chemistry, M2 Macrophage, 3. Good health, macrophages, Phenotype, Arachidonic acid, Docosahexaenoic acid, Fatty Acids, Unsaturated, ω-3, infection, Omega-3 fatty acids, Fatty acid metabolism, arachidonic acid, eicosanoids, omega-3, Infection, Polyunsaturated fatty acid, cytochrome P450, Macrophage polarization, CHO Cells, QD415-436, Biotechnologies, Host-Parasite Interactions, 03 medical and health sciences, Cricetulus, Animals, [CHIM.COOR]Chemical Sciences/Coordination chemistry, Macrophages, Cell Biology, [CHIM.COOR] Chemical Sciences/Coordination chemistry, biology.organism_classification, Mice, Inbred C57BL, 030104 developmental biology, Metabolism, biology.protein, Eicosanoids, metabolism
Abstract: International audience; Inside the human host, Leishmania infection starts with phagocytosis of infective promastigotes by macrophages. In order to survive, Leishmania has developed several strategies to manipulate macrophage functions. Among these strategies, Leishmania as a source of bioactive lipids has been poorly explored. Herein, we assessed the biosynthesis of polyunsaturated fatty acid metabolites by infective and noninfective stages of Leishmania and further explored the role of these metabolites in macrophage polarization. The concentration of docosahexaenoic acid metabolites, precursors of proresolving lipid mediators, was increased in the infective stage of the parasite compared with the noninfective stage, and cytochrome P450-like proteins were shown to be implicated in the biosynthesis of these metabolites. The treatment of macrophages with lipids extracted from the infective forms of the parasite led to M2 macrophage polarization and blocked the differentiation into the M1 phenotype induced by IFN-γ. In conclusion, Leishmania polyunsaturated fatty acid metabolites, produced by cytochrome P450-like protein activity, are implicated in parasite/host interactions by promoting the polarization of macrophages into a proresolving M2 phenotype.
Published: 2019
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39. Nod2 protects remote small intestinal sites in case of colonic inflammation

Author: C. Madre, Nicolas Montcuquet, Camille Jung, Dominique Berrebi, Monique Dussaillant, Nadine Cerf-Bensussan, Jean-Pierre Hugot, Frédérick Barreau, Habib Zouali, Eric Ogier-Denis, Jerrold R. Turner, Z. Al Nabhani, Christine Martinez-Vinson, G. Singh, Gilles Dietrich, Maryline Roy, Fanny Daniel, CRI UMR 1149, Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5), Institut de Recherche en Santé Digestive (IRSD ), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Brigham and Women's Hospital, Partenaires INRAE, Fondation Jean Dausset, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), and ProdInra, Migration
Subjects: [SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT], Inflammation, chain, Biology, kinase/CD4+ 30 T cells, permeability/Crohn's, barrier/myosin, 03 medical and health sciences, 0302 clinical medicine, Duodenitis, Downregulation and upregulation, NOD2, medicine, Ileitis, Kinase activity, 030304 developmental biology, 0303 health sciences, [SDV.OT] Life Sciences [q-bio]/Other [q-bio.OT], disease/gut, Acquired immune system, medicine.disease, Nod2/intestinal, light, digestive system diseases, 3. Good health, Cancer research, 030211 gastroenterology & hepatology, medicine.symptom, Stem cell, Autre (Sciences du Vivant)
Abstract: NOD2 mutations are key risk factors for Crohn’s disease (CD). NOD2 contributes to intestinal homeostasis by regulating innate and adaptive immunity together with intestinal epithelial function. However, the roles of NOD2 during gut inflammation is not known. We initially observed that NOD2 expression was increased in epithelial cells remote from inflamed areas in CD patients. To explore this finding, Nod2 mRNA expression, inflammation and gut permeability were examined in the small bowel of wild-type (WT), Nod2 knockout and Nod2 mutant mice after rectal instillation of 2,4,6-trinitrobenzene sulfonic acid (TNBS). In WT mice, Nod2 upregulation remote to rectal injury was associated with pro-inflammatory cytokine expression, recirculating CD4+ T-cells, increased paracellular permeability and myosin like chain kinase activity. Nod2 knockout or mutation led to duodenitis and ileitis demonstrating the remote protective role of Nod2. Bone morrow stem cell (BMSC) transplantations indicated that the small intestinal inflammation was due to NOD2 loss in both hematopoietic and non-hematopoietic compartments. As a whole, WT but not mutant NOD2 prevents disease extension at sites remote from the initial intestinal injury.
Published: 2019
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40. Multiple primary malignancies: synchronous lymphoma, pancreatic neuroendocrine tumour and colorectal cancer

Author: Gilles Dietrich, Nicolas Dayer, François Fasquelle, and Emanuela Salati
Subjects: medicine.medical_specialty, Colorectal cancer, medicine.medical_treatment, pancreatic cancer, Case Report, 030209 endocrinology & metabolism, Neoplasms, Multiple Primary, Polymyalgia rheumatica, surgical oncology, 03 medical and health sciences, 0302 clinical medicine, Surgical oncology, Positron Emission Tomography Computed Tomography, Pancreatic cancer, Pancreatic mass, medicine, Humans, Aged, Chemotherapy, business.industry, endocrine cancer, General Medicine, medicine.disease, Neuroendocrine tumour, Lymphoma, Pancreatic Neoplasms, colon cancer, 030220 oncology & carcinogenesis, pathology, Female, Lymphoma, Large B-Cell, Diffuse, Radiology, Colorectal Neoplasms, business
Abstract: A 67-year-old woman underwent a medical check-up by her general practitioner after complaining of atypical pain in the shoulder girdle. Due to the important inflammatory syndrome noticed on blood testing, a polymyalgia rheumatica was suspected and she was started on corticosteroid treatment with good clinical response, but no impact on inflammation. She underwent extensive imaging with a thoraco-abdominal CT scanner that demonstrated a pancreatic mass, then later a PET-CT showed 3 different hyperactive lesions. Biopsies then revealed simultaneous diffuse large B-cell lymphoma (DLBCL), colorectal adenocarcinoma and pancreatic neuroendocrine tumour. She benefited from low rectal endoscopic excision of the colorectal tumour, R-CHOP chemotherapy for DLBCL and laparoscopic left pancreatectomy. Successful treatment required a good multidisciplinary collaboration between the different specialists. The patient made a good recovery and achieved complete remission at 1 year. This an unusual presentation of multiple primary malignancies.
Published: 2021
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41. Fluoro-registered Mazor X stealth edition versus O-arm navigation: Preliminary results of the first 21 patients

Author: Didier Grasset, Sébastien Lévy, Marc Prod’homme, Gilles Dietrich, Duccio Boscherini, and Lionel Helfer
Subjects: business.industry, Medicine, Neurology. Diseases of the nervous system, RC346-429, business, Nuclear medicine
Published: 2021
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42. 5-oxoETE triggers nociception in constipation-predominant irritable bowel syndrome through MAS-related G protein–coupled receptor D

Author: Nathalie Vergnolle, Tereza Bautzova, Michael M Tranter, Pauline Le Faouder, Maria Raffaella Barbaro, James R.F. Hockley, David C. Bulmer, Helene Eutamene, Corinne Rolland, Alexandre Denadai-Souza, Gilles Dietrich, Ewan St. John Smith, Lilian Basso, Julien Pujo, Nicolas Cenac, Teresa Pérez-Berezo, Giovanni Barbara, David Hughes, Aziz Moqrich, Pascale Malapert, Cleo Desormeaux, Fonctions et dysfonctions épithéliales - UFC (EA 4267) (FDE), Université de Franche-Comté (UFC), Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Dpto di Farmacia e biotecnologie, Université de Bologne, Centre de Physiopathologie Toulouse Purpan ex IFR 30 et IFR 150 (CPTP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie du Développement de Marseille (IBDM), Aix Marseille Université (AMU)-Collège de France (CdF)-Centre National de la Recherche Scientifique (CNRS), Neuro-Gastroentérologie et Nutrition (NGN), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole supérieure d'agriculture de Purpan (ESAP), Department of Neuroscience, Max Delbrück Center for Molecular Medicine (MDC), University of Cambridge [UK] (CAM), The London School of Medicine & Dentistry, Queen Mary University London, London, UK, University of Bologna, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Aix Marseille Université (AMU)-Collège de France (CdF (institution))-Centre National de la Recherche Scientifique (CNRS), Neuro-Gastroentérologie & Nutrition (ToxAlim-NGN), ToxAlim (ToxAlim), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), University of Glasgow, Bautzova, Tereza, Hockley, James R.F., Perez-Berezo, Teresa, Pujo, Julien, Tranter, Michael M., Desormeaux, Cleo, Barbaro, Maria Raffaella, Basso, Lilian, Le Faouder, Pauline, Rolland, Corinne, Malapert, Pascale, Moqrich, Aziz, Eutamene, Helene, Denadai-Souza, Alexandre, Vergnolle, Nathalie, Smith, Ewan St John, Hughes, David I., Barbara, Giovanni, Dietrich, Gille, Bulmer, David C., Cenac, Nicolas, Poulain, Sébastien, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), University of Bologna/Università di Bologna, Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT), and ANR-17-CE16-0020,Myochronic,Etude des mécanismes moléculaires qui sous-tendent la chronicisation de la douleur. Ce qu'une Myosine non conventionnelle nous apprend(2017)
Subjects: Male, Nociception, 0301 basic medicine, 5-OXO-6,8,11,14-EICOSATETRAENOIC ACID, Abdominal pain, INFLAMMATORY PAIN, [SDV]Life Sciences [q-bio], Biochemistry, Receptors, G-Protein-Coupled, Irritable Bowel Syndrome, Mice, 0302 clinical medicine, Dorsal root ganglion, RESOLVIN D1, Ganglia, Spinal, Receptor, Irritable bowel syndrome, POLYUNSATURATED FATTY-ACIDS, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, Gastrointestinal disorder, medicine.symptom, VISCERAL PAIN, SPINAL-CORD, Life Sciences & Biomedicine, Signal Transduction, medicine.medical_specialty, Biochemistry & Molecular Biology, Sensory Receptor Cells, Colon, LIPID MEDIATOR, Inflammation, Arachidonic Acids, Article, 03 medical and health sciences, Internal medicine, POTENTIAL CHANNELS, medicine, KCNQ/M-CURRENTS, Animals, Humans, Molecular Biology, Science & Technology, Phospholipase C, business.industry, Cell Biology, medicine.disease, Mice, Inbred C57BL, 030104 developmental biology, Endocrinology, Case-Control Studies, SENSORY NEURONS, Calcium, business, Constipation, 030217 neurology & neurosurgery
Abstract: Irritable bowel syndrome (IBS) is a common gastrointestinal disorder that is characterized by chronic abdominal pain concurrent with altered bowel habit. Polyunsaturated fatty acid (PUFA) metabolites are increased in abundance in IBS and are implicated in the alteration of sensation to mechanical stimuli, which is defined as visceral hypersensitivity. We sought to quantify PUFA metabolites in patients with IBS and evaluate their role in pain. Quantification of PUFA metabolites by mass spectrometry in colonic biopsies showed an increased abundance of 5-oxoeicosatetraenoic acid (5-oxoETE) only in biopsies taken from patients with IBS with predominant constipation (IBS-C). Local administration of 5-oxoETE to mice induced somatic and visceral hypersensitivity to mechanical stimuli without causing tissue inflammation. We found that 5-oxoETE directly acted on both human and mouse sensory neurons as shown by lumbar splanchnic nerve recordings and Ca2+ imaging of dorsal root ganglion (DRG) neurons. We showed that 5-oxoETE selectively stimulated nonpeptidergic, isolectin B4 (IB4)-positive DRG neurons through a phospholipase C (PLC)- and pertussis toxin-dependent mechanism, suggesting that the effect was mediated by a G protein-coupled receptor (GPCR). The MAS-related GPCR D (Mrgprd) was found in mouse colonic DRG afferents and was identified as being implicated in the noxious effects of 5-oxoETE. Together, these data suggest that 5-oxoETE, a potential biomarker of IBS-C, induces somatic and visceral hyperalgesia without inflammation in an Mrgprd-dependent manner. Thus, 5-oxoETE may play a pivotal role in the abdominal pain associated with IBS-C. ispartof: SCIENCE SIGNALING vol:11 issue:561 ispartof: location:United States status: published
Published: 2018
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43. Effect of robotic-assisted gait rehabilitation on dynamic equilibrium control in the gait of children with cerebral palsy

Author: Laura Wallard, Gilles Dietrich, Y. Kerlirzin, J. Bredin, Laboratoire d'Automatique, de Mécanique et d'Informatique industrielles et Humaines - UMR 8201 (LAMIH), Université de Valenciennes et du Hainaut-Cambrésis (UVHC)-Centre National de la Recherche Scientifique (CNRS)-INSA Institut National des Sciences Appliquées Hauts-de-France (INSA Hauts-De-France), Education Discours Apprentissages (EDA - EA 4071), Université Paris Descartes - Paris 5 (UPD5), Université Côte d'Azur, LAMHESS, and UCL - SSS/IREC/NMSK - Neuro-musculo-skeletal Lab
Subjects: Male, 030506 rehabilitation, medicine.medical_specialty, Motion analysis, Orthotic Devices, Robotic assisted, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Population, Biophysics, Walking, Cerebral palsy, Clinical gait analysis, 03 medical and health sciences, 0302 clinical medicine, Gait training, Center of pressure (terrestrial locomotion), Medicine, Humans, Orthopedics and Sports Medicine, education, Child, Gait, Gait Disorders, Neurologic, Treated group, education.field_of_study, Analysis of Variance, Rehabilitation, business.industry, Robotic rehabilitation, Cerebral Palsy, Robotics, medicine.disease, Exercise Therapy, Kinetics, Dynamic equilibrium control, Physical therapy, Female, 0305 other medical science, business, human activities, 030217 neurology & neurosurgery
Abstract: International audience; Due to the intensity and repetition of movement, roboticassisted gait training therapy could have a beneficial effect on the recovery and improvement of postural and locomotor functions of the patient. This study sought to highlight the effects of robotic-assisted gait rehabilitation in gait of children with Cerebral Palsy (CP). We analyzed the different strategies before and after this rehabilitation which was used in order to generate forward motion while maintaining balance. Data were collected by a motion analysis system (Vicon® - Oxford Metrics, Oxford, UK). The children were divided into two groups in such a way as to obtain a randomized controlled population: i) a group of fourteen children (Treated Group) underwent 20 sessions of roboticassisted gait training therapy using the driven gait orthosis Lokomat®Pediatric (Hocoma AG, Volketswil, Switzerland) compared to ii) a group of sixteen children without sessions of Lokomat®Pediatric (Control Group). Significant differences are observed for the TG between the preand post-test values of the locomotor parameters and of the kinetic data of the propulsive forces of the Center of Mass (COM) and of the Center of Pressure (COP) dynamic trajectory. This first study, although performed on a limited number of patients, shows the usefulness of this robotic gait rehabilitation mainly in the balance control in gait. Indeed after this rehabilitation, these children improve their gait that is especially characterized by a more appropriate time lag between the time instant of COM-COP trajectory divergence and the time instant when the forward propulsive forces became apparent.
Published: 2018
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44. Intestinal inflammation and pain management

Author: Arnaud Bourreille, Gilles Dietrich, and Lilian Basso
Subjects: Pharmacology, business.industry, Effector, T-Lymphocytes, Models, Immunological, Endogeny, Sensory system, Visceral pain, Visceral Pain, Inflammatory Bowel Diseases, Analgesics, Opioid, Opioid Peptides, Opioid, Drug Discovery, Immunology, Humans, Pain Management, Medicine, medicine.symptom, business, Opioid peptide, Receptor, medicine.drug, Endogenous opioid
Abstract: Intestinal inflammation results in the production of inflammatory pain-inducing mediators that may directly activate colon sensory neurons. Endogenous opioids produced by mucosal effector CD4(+) T lymphocytes identified as colitogenic may paradoxically counterbalance the local pro-algesic effect of inflammatory mediators by acting on opioid receptors expressed on sensory nerve endings. The review will focus on the endogenous immune-mediated regulation of visceral inflammatory pain, current pain treatments in inflammatory bowel diseases and prospectives on new opioid therapeutic opportunities to alleviate pain but avoiding common centrally-mediated side effects.
Published: 2015
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45. Effects of robotic gait rehabilitation on biomechanical parameters in the chronic hemiplegic patients

Author: L. Wallard, Y. Kerlirzin, J. Bredin, Gilles Dietrich, Laboratoire d'Automatique, de Mécanique et d'Informatique industrielles et Humaines - UMR 8201 (LAMIH), Université de Valenciennes et du Hainaut-Cambrésis (UVHC)-Centre National de la Recherche Scientifique (CNRS)-INSA Institut National des Sciences Appliquées Hauts-de-France (INSA Hauts-De-France), Education Discours Apprentissages (EDA - EA 4071), Université Paris Descartes - Paris 5 (UPD5), Laboratoire Motricité Humaine Education Sport Santé, Université Nice Sophia Antipolis (... - 2019) (UNS), and COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)
Subjects: Male, 030506 rehabilitation, Knee Joint, "Cinématique du genou", [SDV]Life Sciences [q-bio], medicine.medical_treatment, Knee kinematics, Walking, " Orthèse de marche", 0302 clinical medicine, Gait (human), Stroke, "Paramètres locomoteurs", Rehabilitation, Stroke Rehabilitation, Robotics, General Medicine, Middle Aged, "Locomotor parameters", Biomechanical Phenomena, Neurology, Female, 0305 other medical science, Psychology, medicine.medical_specialty, Motion analysis, Hemiplegia, "Gait rehabilitation", 03 medical and health sciences, Physical medicine and rehabilitation, "Rééducation de la marche", Physiology (medical), medicine, Humans, Knee, Gait Disorders, Neurologic, Aged, "Chronic hemiplegic", "Driven gait orthosis", medicine.disease, "Hémiplégie chronique", "Knee kinematics", body regions, Preferred walking speed, Gait analysis, Chronic Disease, Physical therapy, Neurology (clinical), human activities, 030217 neurology & neurosurgery
Abstract: IF=2.752; International audience; Hemiplegia is a more or less complete loss of hemibody voluntary motricity following a brain injury, usually resulting in alterations of the locomotor system with persistent disorders of movement and posture. We were interested in studying the gait pattern called "stiff knee gait" with the main objective to highlight the role of a robotic rehabilitation in improving or modifying/changing the walking pattern in adults with chronic hemiplegic disorders. Data were collected by a motion analysis system (Vicon(®)--Oxford Metrics, Oxford, UK) in order to achieve a Clinical Gait Analysis before and after a robotic gait rehabilitation (Lokomat(®)). Four intensive sessions per weeks during five weeks were performed by ten chronic hemiplegic adults. The results show a significant improvement in locomotor parameters (walking speed, step length, single and double support time) and in the knee kinematics. This first study provides experimental evidence of the importance and usefulness of the robotic rehabilitation as an aid in the rehabilitation of gait pattern in adults with chronic hemiplegia
Published: 2015
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46. Learning to tune the antero-posterior propulsive forces during walking: a necessary skill for mastering upright locomotion in toddlers

Author: Gilles Dietrich, Daniela Corbetta, Blandine Bril, and Lucile Dupuy
Subjects: Male, Communication, medicine.medical_specialty, Motion analysis, Computer science, business.industry, General Neuroscience, Lower limb kinematics, Centre of pressure, Follow up studies, Infant, Walking, Kinematics, Biomechanical Phenomena, Child Development, Physical medicine and rehabilitation, medicine, Humans, Learning, Female, business, human activities, Follow-Up Studies
Abstract: This study examines the process of learning to walk from a functional perspective. To move forward, one must generate and control propulsive forces. To achieve this, it is necessary to create and tune a distance between the centre of mass (CoM) and the centre of pressure (CoP) along the antero-posterior axis. We hypothesize that learning to walk consists of learning how to calibrate these self-generated propulsive forces to control such distance. We investigated this question with six infants (three girls and three boys) who we followed up weekly for the first 8 weeks after the onset of walking and then biweekly until they reached 14-16 weeks of walking experience. The infants' walking patterns (kinematics and propelling forces) were captured via synched motion analysis and force plate. The results show that the distance between the CoM and the CoP along the antero-posterior axis increased rapidly during the first months of learning to walk and that this increase was correlated with an increase in velocity. The initial small values of (CoM-CoP) observed at walking onset, coupled with small velocity are interpreted as the solution infants adopted to satisfy a compromise between the need to generate propulsive forces to move forward while simultaneously controlling the disequilibrium resulting from creating a with distance between the CoM and CoP.
Published: 2015
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47. 5. Habiletés impliquées dans la taille des perles en calcédoine : caractéristiques motrices et cognitives d’une action située complexe

Author: Blandine Bril, Gilles Dietrich, and Valentine Roux
Subjects: History
Published: 2017
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48. 5. Skills involved in the knapping of chalcedony beads: Motor and cognitive characteristics of a complex situated action

Author: Blandine Bril, Gilles Dietrich, and Valentine Roux
Subjects: Cognitive science, Communication, Chalcedony, Action (philosophy), Knapping, business.industry, Situated, engineering, Cognition, engineering.material, business, Psychology
Published: 2017
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49. Nod2: The intestinal gate keeper

Author: Jean-Pierre Hugot, Gilles Dietrich, Ziad Al Nabhani, Frédérick Barreau, CRI UMR 1149, Lab Excellence Inflamex, Université Paris Diderot - Paris 7 (UPD7), Lab Excellence Inflamex, Institut de Recherche en Santé Digestive (IRSD ), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Hop Robert Debre, Assistance Publique - Hôpitaux de Paris, Investissements d'Avenir programme ANR-11-IDEX-0005-02, Sorbonne Paris Cite, Laboratoire d'excellence INFLAMEX, ANR-11-IDEX-0005,USPC,Université Sorbonne Paris Cité(2011), ProdInra, Archive Ouverte, Université Sorbonne Paris Cité - - USPC2011 - ANR-11-IDEX-0005 - IDEX - VALID, Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT)
Subjects: 0301 basic medicine, flore commensale, Nod2 Signaling Adaptor Protein, microbiote digestif, Review, Pathogenesis, Pathology and Laboratory Medicine, chemistry.chemical_compound, 0302 clinical medicine, NOD2, Medicine and Health Sciences, Biology (General), Immune Response, Pattern recognition receptor, Genomics, Animal Models, 3. Good health, Bacterial Pathogens, Intestines, Experimental Organism Systems, Medical Microbiology, 030220 oncology & carcinogenesis, Viral Pathogens, Host-Pathogen Interactions, Viruses, réaction inflammatoire, medicine.symptom, Anatomy, Pathogens, Muramyl dipeptide, host pathogen systems, QH301-705.5, Immunology, Inflammation, Mouse Models, Microbial Genomics, Biology, Research and Analysis Methods, Microbiology, 03 medical and health sciences, Immune system, Model Organisms, Signs and Symptoms, Diagnostic Medicine, Virology, medicine, Genetics, Parasitic Diseases, Animals, Humans, Microbiome, Molecular Biology, Blau syndrome, Microbial Pathogens, commensal flora, Organisms, interaction hôte pathogène, Biology and Life Sciences, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, RC581-607, medicine.disease, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, digestive system diseases, Gastrointestinal Microbiome, Gastrointestinal Tract, Hépatologie et Gastroentérologie, 030104 developmental biology, chemistry, Hépatology and Gastroenterology, Parasitology, Peptidoglycan, Immunologic diseases. Allergy, Parasitic Intestinal Diseases, Digestive System
Abstract: Nucleotide-binding oligomerization domain 2 (NOD2) is an intracellular pattern recognition receptor that senses bacterial peptidoglycan (PGN)-conserved motifs in cytosol and stimulates host immune response. The association of NOD2 mutations with a number of inflammatory pathologies, including Crohn disease (CD), Graft-versus-host disease (GVHD), and Blau syndrome, highlights its pivotal role in host-pathogen interactions and inflammatory response. Stimulation of NOD2 by its ligand (muramyl dipeptide) activates pro- inflammatory pathways such as nuclear factor-kappa B (NF-kappa B), mitogen-activated protein kinases (MAPKs), and Caspase-1. A loss of NOD2 function may result in a failure in the control of microbial infection, thereby initiating systemic responses and aberrant inflammation. Because the ligand of Nod2 is conserved in both gram-positive and gram-negative bacteria, NOD2 detects a wide variety of microorganisms. Furthermore, current literature evidences that NOD2 is also able to control viruses' and parasites' infections. In this review, we present and discuss recent developments about the role of NOD2 in shaping the gut commensal microbiota and pathogens, including bacteria, viruses, and parasites, and the mechanisms by which Nod2 mutations participate in disease occurrence.
Published: 2017
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50. Endogenous Regulation of Visceral Pain via Production of Opioids by Colitogenic CD4+ T Cells in Mice

Author: Gilles Dietrich, Nathalie Vergnolle, Jérôme Boué, Malvyne Rolli–Derkinderen, Nicolas Cenac, Lilian Basso, Catherine Blanpied, and Michel Neunlist
Subjects: Colon, T cell, Myenteric Plexus, Inflammation, Mice, SCID, Biology, Inflammatory bowel disease, Mice, Immune system, Antigen, medicine, Animals, Colitis, Immunity, Mucosal, Endogenous opioid, Mice, Inbred BALB C, Hepatology, Dextran Sulfate, Gastroenterology, Visceral pain, Visceral Pain, Th1 Cells, medicine.disease, Disease Models, Animal, medicine.anatomical_structure, Opioid Peptides, Immunology, Th17 Cells, medicine.symptom
Abstract: Background & Aims A dysregulated response of CD4 + T cells against the microbiota contributes to the development of inflammatory bowel disease. Effector CD4 + T cells, generated in response to microbe-derived antigens, can reduce somatic inflammatory pain through the local release of opioids. We investigated whether colitogenic CD4 + T cells that accumulate in the inflamed colon also produce opioids and are able to counteract inflammation-induced visceral pain in mice. Methods Colitis was induced via transfer of naive CD4 + CD45RB high T cells to immune-deficient mice or by administration of dextran sulfate sodium. Mice without colitis were used as controls. Samples of colon tissue were collected, and production of opioids by immune cells from inflamed intestine was assessed by quantitative polymerase chain reaction and cytofluorometry analyses. The role of intestinal opioid tone in inflammation-induced visceral hypersensitivity was assessed by colorectal distention. Results In mice with T cell– or dextran sulfate sodium–induced colitis, colitogenic CD4 + T cells (T-helper 1 and Th17 cells) accumulated in the inflamed intestine and expressed a high level of endogenous opioids. In contrast, macrophages and epithelial cells did not express opioids; opioid synthesis in the myenteric plexus was not altered on induction of inflammation. In mice with colitis, the local release of opioids by colitogenic CD4 + T cells led to significant reduction of inflammation-associated visceral hypersensitivity. Conclusions In mice, colitogenic Th1 and Th17 cells promote intestinal inflammation and colonic tissue damage but have simultaneous opioid-mediated analgesic activity, thereby reducing abdominal pain.
Published: 2014
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