Institut Universitaire de France

Paris, France

Institut Universitaire de France

Paris, France
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Desmedt A.,Institut Universitaire de France | Marighetto A.,Institut Universitaire de France | Piazza P.-V.,Institut Universitaire de France
Biological Psychiatry | Year: 2015

Abstract For over a century, clinicians have consistently described the paradoxical co-existence in posttraumatic stress disorder (PTSD) of sensory intrusive hypermnesia and declarative amnesia for the same traumatic event. Although this amnesia is considered as a critical etiological factor of the development and/or persistence of PTSD, most current animal models in basic neuroscience have focused exclusively on the hypermnesia, i.e., the persistence of a strong fear memory, neglecting the qualitative alteration of fear memory. The latest is characterized by an underrepresentation of the trauma in the context-based declarative memory system in favor of its overrepresentation in a cue-based sensory/emotional memory system. Combining psychological and neurobiological data as well as theoretical hypotheses, this review supports the idea that contextual amnesia is at the core of PTSD and its persistence and that altered hippocampal-amygdalar interaction may contribute to such pathologic memory. In a first attempt to unveil the neurobiological alterations underlying PTSD-related hypermnesia/amnesia, we describe a recent animal model mimicking in mice some critical aspects of such abnormal fear memory. Finally, this line of argument emphasizes the pressing need for a systematic comparison between normal/adaptive versus abnormal/maladaptive fear memory to identify biomarkers of PTSD while distinguishing them from general stress-related, potentially adaptive, neurobiological alterations. © 2015 Society of Biological Psychiatry


Guyon A.,Institut Universitaire de France
Frontiers in Cellular Neuroscience | Year: 2014

The chemokine CXCL12/stromal cell-derived factor 1 alpha has first been described in the immune system where it functions include chemotaxis for lymphocytes and macrophages, migration of hematopoietic cells from fetal liver to bone marrow and the formation of large blood vessels. Among other chemokines, CXCL12 has recently attracted much attention in the brain as it has been shown that it can be produced not only by glial cells but also by neurons. In addition, its receptors CXCR4 and CXCR7, which are belonging to the G protein-coupled receptors family, are abundantly expressed in diverse brain area, CXCR4 being a major co-receptor for human immunodeficiency virus 1 entry. This chemokine system has been shown to play important roles in brain plasticity processes occurring during development but also in the physiology of the brain in normal and pathological conditions. For example, in neurons, CXCR4 stimulation has been shown regulate the synaptic release of glutamate and y-aminobutyricacid (GABA). It can also act post-synaptically by activating a G protein activated inward rectifier K+ (GIRK), a voltage-gated K channel Kv2.1 associated to neuronal survival, and by increasing high voltage activated Ca2+ currents. In addition, it has been recently evidenced that there are several cross-talks between the CXCL12/CXCR4-7 system and other neurotransmitter systems in the brain (such as GABA, glutamate, opioids, and cannabinoids). Overall, this chemokine system could be one of the key players of the neuro-immune interface that participates in shaping the brain in response to changes in the environment. © 2014 Guyon.


Mabilleau G.,Institut Universitaire de France
Current Opinion in Pharmacology | Year: 2015

To adapt to its various functions, the bone tissue is remodeled permanently and is under the influence of hormonal, local, mechanical and nervous signals. Among them, a role for gut hormones in controlling bone mass and quality has emerged in the recent years. The aim of this review is to provide the reader with a summary of recent developments in the interaction between incretin hormones and bone physiology. © 2015 Elsevier Ltd.


Guillemot F.,UK National Institute for Medical Research | Zimmer C.,Institut Universitaire de France
Neuron | Year: 2011

The generation of a functional nervous system involves a multitude of steps that are controlled by just a few families of extracellular signaling molecules. Among these, the fibroblast growth factor (FGF) family is particularly prominent for the remarkable diversity of its functions. FGFs are best known for their roles in the early steps of patterning of the neural primordium and proliferation of neural progenitors. However, other equally important functions have emerged more recently, including in the later steps of neuronal migration, axon navigation, and synaptogenesis. We review here these diverse functions and discuss the mechanisms that account for this unusual range of activities. FGFs are essential components of most protocols devised to generate therapeutically important neuronal populations in vitro or to stimulate neuronal repair in vivo. How FGFs promote the development of the nervous system and maintain its integrity will thus remain an important focus of research in the future. © 2011 Elsevier Inc.


Alix-Panabieres C.,Montpellier University Hospital Center | Alix-Panabieres C.,Institut Universitaire de France | Pantel K.,University of Hamburg
Nature Reviews Cancer | Year: 2014

During the past ten years, circulating tumour cells (CTCs) have received enormous attention as new biomarkers and the subject of basic research. Although CTCs are already used in numerous clinical trials, their clinical utility is still under investigation. Many issues regarding the detection and characterization of CTCs remain unknown. In this Opinion article, we propose a conceptual framework of CTC assays and point out current challenges of CTC research, which might structure this dynamic field of translational cancer research. © 2014 Macmillan Publishers Limited.


Indirect nuclear spin-spin coupling involving very commonly encountered nuclei such as 1H, 13C, 19F, or 31P provides definitive data for characterization of molecules in solution. Nonbonded spin coupling characterized by high magnitude values have been repeatedly authenticated for a range of compounds such as functionalized cyclophanes, naphthalenes, coordination complexes of polyphosphines, as well as fluorinated arene complexes. The range of applications in chemistry and structural biology involving a 19F NMR probe proves that TS spin coupling with this nucleus can be a valuable additional tool in pursuing structural questions. Analysis of TS 19F coupling in fluorinated organic molecules, but also in amino acids, proteins, nucleic acids, and nucleic acid-protein complexes can inform us regarding the differentiation of rotamers and diastereoisomers, estimation of internuclear distances, computation of tertiary and quaternary structures, as well as understanding of dynamic processes involved in solution.


Romero N.B.,Institut Universitaire de France
Acta neuropathologica communications | Year: 2014

Nemaline myopathy (NM) is a rare congenital myopathy characterised by hypotonia, muscle weakness, and often skeletal muscle deformities with the presence of nemaline bodies (rods) in the muscle biopsy. The nebulin (NEB) gene is the most commonly mutated and is thought to account for approximately 50% of genetically diagnosed cases of NM. We undertook a detailed muscle morphological analysis of 14 NEB-mutated NM patients with different clinical forms to define muscle pathological patterns and correlate them with clinical course and genotype. Three groups were identified according to clinical severity. Group 1 (n = 5) comprises severe/lethal NM and biopsy in the first days of life. Group 2 (n = 4) includes intermediate NM and biopsy in infancy. Group 3 (n = 5) comprises typical/mild NM and biopsy in childhood or early adult life. Biopsies underwent histoenzymological, immunohistochemical and ultrastructural analysis. Fibre type distribution patterns, rod characteristics, distribution and localization were investigated. Contractile performance was studied in muscle fibre preparations isolated from seven muscle biopsies from each of the three groups. G1 showed significant myofibrillar dissociation and smallness with scattered globular rods in one third of fibres; there was no type 1 predominance. G2 presented milder sarcomeric dissociation, dispersed or clustered nemaline bodies, and type 1 predominance/uniformity. In contrast, G3 had well-delimited clusters of subsarcolemmal elongated rods and type 1 uniformity without sarcomeric alterations. In accordance with the clinical and morphological data, functional studies revealed markedly low forces in muscle bundles from G1 and a better contractile performance in muscle bundles from biopsies of patients from G2, and G3.In conclusion NEB-mutated NM patients present a wide spectrum of morphological features. It is difficult to establish firm genotype phenotype correlation. Interestingly, there was a correlation between clinical severity on the one hand and the degree of sarcomeric dissociation and contractility efficiency on the other. By contrast the percentage of fibres occupied by rods, as well as the quantity and the sub sarcolemmal position of rods, appears to inversely correlate with severity. Based on our observations, we propose myofibrillar dissociation and changes in contractility as an important cause of muscle weakness in NEB-mutated NM patients.


Gluckman E.,Institut Universitaire de France
Blood Reviews | Year: 2011

Since the first human cord blood transplant, performed in 1988, cord blood banks have been established worldwide for collection and cryopreservation of cord blood for allogeneic hematopoietic stem cell transplant. Umbilical cord blood (UCB) has now become one of the most commonly used source of hematopoietic stem cells for allogeneic transplantation. Today a global network of cord blood banks and transplant centers has been established for a common inventory with an estimated 600,000 UCB have been banked and more than 20,000 UCB units distributed worldwide for adults and children with severe hematological diseases. Several studies have shown that the number of cells is the most important factor for engraftment while some degree of HLA mismatches is acceptable. The absence of ethical concern, and the unlimited supply of cells explain the increasing interest of using cord blood for developing regenerative medicine. © 2011 Elsevier Ltd.


Kerneis M.,Institut Universitaire de France
JACC. Cardiovascular interventions | Year: 2013

This study sought to assess the consequences of switching prasugrel to clopidogrel on platelet inhibition and clinical outcomes after an acute coronary syndrome (ACS). Many ACS patients are switched from prasugrel to clopidogrel within the recommended 1-year duration of treatment. Platelet reactivity was measured with the VerifyNow P2Y(12) assay (Accumetrics, San Diego, California) in 300 ACS patients treated for 15 days with prasugrel 10 mg. Patients displaying low on-treatment platelet reactivity (LPR) and/or at high risk of bleeding were switched to clopidogrel 75 mg and tested again 15 days later. The rate of patients with high on-treatment platelet reactivity (HPR), P2Y(12) reaction units (PRU) >208, and LPR (PRU <0) were evaluated before and after the switch. Bleeding and ischemic events were also recorded. On a regimen of prasugrel 10 mg, the rate of patients with LPR was 45.6% (n = 137), whereas 4.3% (n = 13) had HPR. A group of 31 patients (10.3%) was switched to clopidogrel 75 mg, of whom 29 had LPR (93.5%) on a regimen of prasugrel. On-treatment platelet reactivity (PRU) increased from 14 ± 4 on a regimen of prasugrel to 155 ±15 on a regimen of clopidogrel (p = 0.0001), resulting in a much lower rate of patients with LPR (9.7%). The rate of patients with HPR increased from 0% with prasugrel to 29% (n = 9) with clopidogrel. The rate of minor bleeding decreased after the switch from 32.2% to 9.7%; p = 0.03. An LPR is frequent in patients treated with prasugrel 10 mg. Early switching from prasugrel 10 mg to clopidogrel 75 mg reduces the number of patients with LPR and minor bleeding events but unmasks a group of nonresponders to clopidogrel with unknown consequences on clinical outcomes. Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.


Tall A.R.,Columbia University | Yvan-Charvet L.,Institut Universitaire de France
Nature Reviews Immunology | Year: 2015

Hypercholesterolaemia leads to cholesterol accumulation in macrophages and other immune cells, which promotes inflammatory responses, including augmentation of Toll-like receptor (TLR) signalling, inflammasome activation, and the production of monocytes and neutrophils in the bone marrow and spleen. On a cellular level, activation of TLR signalling leads to decreased cholesterol efflux, which results in further cholesterol accumulation and the amplification of inflammatory responses. Although cholesterol accumulation through the promotion of inflammatory responses probably has beneficial effects in the response to infections, it worsens diseases that are associated with chronic metabolic inflammation, including atherosclerosis and obesity. Therapeutic interventions such as increased production or infusion of high-density lipoproteins may sever the links between cholesterol accumulation and inflammation, and have beneficial effects in patients with metabolic diseases. © 2015 Macmillan Publishers Limited. All rights reserved.

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