Les lésions médullaires traumatiques : épidémiologie et perspectives

AbstractObjectiveSpecify the epidemiological data on the acute spinal cord injuries and define a group of patients that could benefit from cellular transplantation therapy designed with the aim of repair and regeneration of damaged spinal cord tissues.Material and methodsFive years monocentric (Gui-de-Chauliac Hospital, Montpellier, France) retrospective analysis of patients suffering from spinal cord injury (SCI). Spinal cord injured-patients, defined as sensory-motor complete, underwent a clinical evaluation following American Spinal Injury Association (ASIA) and functional type 2 Spinal Cord Independence Measure (SCIM2) scorings as well as radiological evaluation through spinal cord magnetic resonance imaging (MRI).ResultsOne hundred and fifty-seven medical records were reviewed and we selected and re-examined 20 patients with complete thoracic spinal cord lesion. Clinical and radiological evaluations of these patients demonstrated, in 75 % of the cases, an absence of clinical progression after a mean of 49months. Radiological abnormalities were constantly present in the initial (at the admission to hospital) and control (re-evaluation) MRI and no reliable predictive criteria of prognosis had been found.Discussion/ConclusionWe compare our results to the literature and discuss advantages and limits of cellular transplantation strategies for these patients.RésuméObjectifsConnaître les données épidémiologiques de notre région sanitaire sur les traumatismes médullaires. Au sein de cette population, sélectionner les patients susceptibles de bénéficier de thérapie cellulaire dans la moelle épinière lésée dans l’objectif de régénérer le tissu nerveux. Évaluer à distance ces patients.Patients et méthodeAnalyse rétrospective de tous les patients pris en charge pour un traumatisme vertébro-médullaire. Réévaluation clinique et radiologique des patients présentant une atteinte médullaire thoracique sensitivomotrice complète. Réévaluation réalisée par le score de l’American Spinal Injury Association (ASIA), le score fonctionnel Type 2 Spinal Cord Independence Measure (SCIM2) et contrôle radiologique par une IRM médullaire.RésultatsCent cinquante-sept dossiers de patients ont été analysés et 28 patients présentaient une lésion médullaire complète. Une évaluation clinique et radiologique réalisée chez 20 patients sur 28 (71 %) a montré l’absence d’évolution clinique dans 75 % des cas dans un délai moyen de 49 mois. Les anomalies radiologiques étaient présentes dans 100 % des cas sur l’IRM initiale et de contrôle sans qu’aucun critère fiable prédictif de bon pronostic n’est retrouvé.Discussion/conclusionNous présentons ces résultats comparativement à ceux de la littérature et nous discutons chez ces malades les stratégies de transplantation cellulaire, leurs limites actuelles et les progrès nécessaires pour obtenir des résultats

Functionnally asynchronous VLSI cellular array for morphological filtering of images

The design of a fine grain asynchronous VLSI cellular array is presented . It is shown how asynchronism can be exploited at both functional and structural levels . A joint algorithmic-architectural study has led to the fabrication of an integrated circuit including 16x16 processing elements .The data and control paths are designed using a standard-cell approach, combining CMOS and DCVSL (Differential Cascode Voltage Switch Logic) gates . The 800,000 transistor circuit enables real time morphological filtering of images.A travers la présentation de la conception d'un réseau cellulaire VLSI asynchrone à grain fin, il est montré comment la notion d'asynchronisme peut être exploitée à la fois au niveau fonctionnel et au niveau architectural. Une étude conjointe algorithme-architecture a abouti à la conception d'un circuit intégrant 16x16 processeurs élémentaires, Le flot de conception des chemins de données et de contrôle est basé sur une approche « cellules standard » qui combine des portes CMOS et DCVSL (Differential Cascode Voltage Switch Logic). Ce circuit d'environ 800.000 transistors permet de mettre en oeuvre en temps réel des algorithmes itératifs de filtrage morphologique par reconstruction

In-situ fines migration and grains redistribution induced by mineral reactions – Implications for clogging during water injection in carbonate aquifers

Water injection into an aquifer is generally motivated by one of three objectives: disposal, managed aquifer recharge (MAR), or aquifer storage and recovery (ASR). Any of these would be undermined if an injection well were to become clogged. This paper investigates whether mineral reactions can cause mobilization of fines and rock grains, and if so, how this would affect clogging. Injection experiments are performed on Edwards Brown (dolomite) and Indiana limestone core samples. X-ray Powder Diffraction analysis of the rocks shows that no clays are present. Filtered-deaired deionized water and pure salts are used to prepare the injection fluids. The core samples are subjected to four sequential injections of fluids: at salinities 44,580 mg/L (referred to as “seawater”), 14,860 mg/L, 7,430 mg/L, and 0 mg/L (deionized water). These salinities are selected to represent disposal, and less saline fluids to represent MAR and ASR projects. Pressure difference is recorded across the core sample at each stage and is used to calculate permeability. The effluent samples are collected to characterize produced fines and elements. The increase in the pH of the effluent samples suggest mineral reactions, which is supported by an increase in the concentration of chemical elements in the effluent samples. Scanning Electron Microscopy (SEM) images show pore enlargement due to dissolution and depict pore blockage due to fines migration, grains redistribution, and mineral precipitation. Mineral reactions dissolved the grain's surface and intergranular cement, releasing silicate fines and rock grains, which in turn reduce the permeability of the rock by 68 % to 99.9 %

Anatomical study of serotonergic innervation and 5-HT1A receptor in the human spinal cord

Serotonergic innervation of the spinal cord in mammals has multiple roles in the control of motor, sensory and visceral functions. In rats, functional consequences of spinal cord injury at thoracic level can be improved by a substitutive transplantation of serotonin (5-HT) neurons or regeneration under the trophic influence of grafted stem cells. Translation to either pharmacological and/or cellular therapies in humans requires the mapping of the spinal cord 5-HT innervation and its receptors to determine their involvement in specific functions. Here, we have performed a preliminary mapping of serotonergic processes and serotonin-lA (5-HT1A) receptors in thoracic and lumbar segments of the human spinal cord. As in rodents and non-human primates, 5-HT profiles in human spinal cord are present in the ventral horn, surrounding motoneurons, and also contact their presumptive dendrites at lumbar level. 5-HT1A receptors are present in the same area, but are more densely expressed at lumbar level. 5-HT profiles are also present in the intermediolateral region, where 5-HT1A receptors are absent. Finally, we observed numerous serotonergic profiles in the superficial part (equivalent of Rexed lamina II) of the dorsal horn, which also displayed high levels of 5-HT1A receptors. These findings pave the way for local specific therapies involving cellular and/or pharmacological tools targeting the serotonergic system

Link-time static analysis for efficient separate compilation of object-oriented languages

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“Savages Who Speak French”: Folklore, Primitivism and Morals in Robert Hertz

Hertz's analysis of the Alpine cult of Saint Besse apparently marks a break from his studies of death, sin and the left to folkloric studies. This analysis helps one to understand the personality of Robert Hertz. His sociological curiosity about folklore reveals his ambiguous position in social sciences at the beginning of the twentieth century. His text appears to be a variation from the Durkheimian norm, but another reading could suggest that Hertz continued and went beyond Durkheimian thought to something between sociology of the modern world and engaged socialism. Through this study, Hertz linked his political ideals, his work in ethnology and his desire for social involvement. The cult of Saint Besse perpetuated as much religious tradition as local identity. The Alpine people were presented in the text as wilful perpetuators of an ideal social order, whose loss for his contemporary city dwellers Hertz feared. The alpine Other, marked by a material and moral backwardness, represented for activist and socialist Hertz one of the paths of balanced social organization that stabilized the identity of a group across time if it fit rather well into the folkloric stereotypes of the beginning of the twentieth century. Finally, by linking events in Herz's life (e.g., the accidental Alpine death of his father), this article suggests that the legend of Saint Besse embodied several recurring motifs in Hertz' career: the accidental deaths of saint and father by falls, the military role of the saint and of Hertz himself

Diabetes-induced mechanical hyperalgesia involves spinal mitogen-activated protein kinase activation in neurons and microglia via N-methyl-D-aspartate-dependent mechanisms

ABSTRACT Molecular mechanisms underlying diabetes-induced painful neuropathy are poorly understood. We have demonstrated, in rats with streptozotocin-induced diabetes, that mechanical hyperalgesia, a common symptom of diabetic neuropathy, was correlated with an early increase in extracellular signal-regulated protein kinase (ERK), p38, and c-Jun N-terminal kinase (JNK) phosphorylation in the spinal cord and dorsal root ganglion at 3 weeks after induction of diabetes. This change was specific to hyperalgesia because nonhyperalgesic rats failed to have such an increase. Immunoblot analysis showed no variation of protein levels, suggesting a post-translational regulation of the corresponding kinases. In diabetic hyperalgesic rats, immunocytochemistry revealed that all phosphorylated mitogen-activated protein kinases (MAPKs) colocalized with both the neuronal (NeuN) and microglial (OX42) cell-specific markers but not with the astrocyte marker [glial fibrillary acidic protein (GFAP)] in the superficial dorsal horn-laminae of the spinal cord. In these same rats, a 7-day administration [5 g/rat/day, intrathecal (i.t.)] of 1,4-diamino-2,3-dicyano-1,4-bis(2-aminophenylthio)butadiene (U0126), 4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)1H-imidazole (SB203580), and anthra(1,9-cd)pyrazol-6(2H)-one (SP600125), which inhibited MAPK kinase, p38, and JNK, respectively, suppressed mechanical hyperalgesia, and decreased phosphorylation of the kinases. To characterize the cellular events upstream of MAPKs, we have examined the role of the NMDA receptor known to be implicated in pain hypersensitivity. The prolonged blockade of this receptor during 7 days by (5R,10S)-(ϩ)-5-methyl-10, 11-dihydro-5H-dibenzo[a,d]-cyclohepten-5-10-imine hydrogen maleate (MK801; 5 g/rat/day, i.t.), a noncompetitive NMDA receptor antagonist, reversed hyperalgesia developed by diabetic rats and blocked phosphorylation of all MAPKs. These results demonstrate for the first time that NMDA receptor-dependent phosphorylation of MAPKs in spinal cord neurons and microglia contribute to the establishment and longterm maintenance of painful diabetic hyperalgesia and that these kinases represent potential targets for pain therapy. Sensitive peripheral neuropathies represent a common and debilitating complication of diabetes (types 1 and 2) and affect an increasing proportion of diabetic patients as the disease progresses. Even though antidepressant and antiepileptic agents have been shown to be partially effective, clinical studies have reported the difficulty of managing pain caused by these neuropathies The mitogen-activated protein kinase (MAPK) cascade is a family of serine/threonine kinases that are activated by dual phosphorylation on threonine and tyrosine residues. The Article, publication date, and citation information can be found a

Grafted Human Embryonic Progenitors Expressing Neurogenin-2 Stimulate Axonal Sprouting and Improve Motor Recovery after Severe Spinal Cord Injury

7 p.Background: Spinal cord injury (SCI) is a widely spread pathology with currently no effective treatment for any symptom. Regenerative medicine through cell transplantation is a very attractive strategy and may be used in different non-exclusive ways to promote functional recovery. We investigated functional and structural outcomes after grafting human embryonic neural progenitors (hENPs) in spinal cord-lesioned rats.Methods and Principal Findings: With the objective of translation to clinics we have chosen a paradigm of delayed grafting, i.e., one week after lesion, in a severe model of spinal cord compression in adult rats. hENPs were either naive or engineered to express Neurogenin 2 (Ngn2). Moreover, we have compared integrating and non-integrating lentiviral vectors, since the latter present reduced risks of insertional mutagenesis. We show that transplantation of hENPs transduced to express Ngn2 fully restore weight support and improve functional motor recovery after severe spinal cord compression at thoracic level. This was correlated with partial restoration of serotonin innervations at lumbar level, and translocation of 5HT1A receptors to the plasma membrane of motoneurons. Since hENPs were not detectable 4 weeks after grafting, transitory expression of Ngn2 appears sufficient to achieve motor recovery and to permit axonal regeneration. Importantly, we also demonstrate that transplantation of naive hENPs is detrimental to functional recovery.Conclusions and Significance: Transplantation and short-term survival of Ngn2-expressing hENPs restore weight support after SCI and partially restore serotonin fibers density and 5HT1A receptor pattern caudal to the lesion. Moreover, grafting of naive-hENPs was found to worsen the outcome versus injured only animals, thus pointing to the possible detrimental effect of stem cell-based therapy per se in SCI. This is of major importance given the increasing number of clinical trials involving cell grafting developed for SCI patients.This study was supported by the European Union FP6 "RESCUE" STREP; the "Institut pour la Recherche sur la Moelle Epiniere"; the "Academie de Medecine"; the "Societe Francaise de Neurochirurgie"; "Verticale" and the "Association Demain Debout Aquitaine". The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

The 'PUCE CAFE' Project: the First 15K Coffee Microarray, a New Tool for Discovering Candidate Genes correlated to Agronomic and Quality Traits

Background: Understanding the genetic elements that contribute to key aspects of coffee biology will have an impact on future agronomical improvements for this economically important tree. During the past years, EST collections were generated in Coffee, opening the possibility to create new tools for functional genomics. Results: The "PUCE CAFE" Project, organized by the scientific consortium NESTLE/IRD/CIRAD, has developed an oligo-based microarray using 15,721 unigenes derived from published coffee EST sequences mostly obtained from different stages of fruit development and leaves in Coffea Canephora (Robusta). Hybridizations for two independent experiments served to compare global gene expression profiles in three types of tissue matter (mature beans, leaves and flowers) in C. canephora as well as in the leaves of three different coffee species (C. canephora, C. eugenoides and C. arabica). Microarray construction, statistical analyses and validation by Q-PCR analysis are presented in this study. Conclusion: We have generated the first 15 K coffee array during this PUCE CAFE project, granted by Genoplante (the French consortium for plant genomics). This new tool will help study functional genomics in a wide range of experiments on various plant tissues, such as analyzing bean maturation or resistance to pathogens or drought. Furthermore, the use of this array has proven to be valid in different coffee species (diploid or tetraploid), drastically enlarging its impact for high-throughput gene expression in the community of coffee research

Characterization, high-resolution mapping and differential expression of three homologous PAL genes in Coffea canephora Pierre (Rubiaceae)

Phenylalanine ammonia lyase (PAL) is the first entry enzyme of the phenylpropanoid pathway producing phenolics, widespread constituents of plant foods and beverages, including chlorogenic acids, polyphenols found at remarkably high levels in the coffee bean and long recognized as powerful antioxidants. To date, whereas PAL is generally encoded by a small gene family, only one gene has been characterized in Coffea canephora (CcPAL1), an economically important species of cultivated coffee. In this study, a molecular- and bioinformatic-based search for CcPAL1 paralogues resulted successfully in identifying two additional genes, CcPAL2 and CcPAL3, presenting similar genomic structures and encoding proteins with close sequences. Genetic mapping helped position each gene in three different coffee linkage groups, CcPAL2 in particular, located in a coffee genome linkage group (F) which is syntenic to a region of Tomato Chromosome 9 containing a PAL gene. These results, combined with a phylogenetic study, strongly suggest that CcPAL2 may be the ancestral gene of C. canephora. A quantitative gene expression analysis was also conducted in coffee tissues, showing that all genes are transcriptionally active, but they present distinct expression levels and patterns. We discovered that CcPAL2 transcripts appeared predominantly in flower, fruit pericarp and vegetative/lignifying tissues like roots and branches, whereas CcPAL1 and CcPAL3 were highly expressed in immature fruit. This is the first comprehensive study dedicated to PAL gene family characterization in coffee, allowing us to advance functional studies which are indispensable to learning to decipher what role this family plays in channeling the metabolism of coffee phenylpropanoids