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

Mechanisms of base selection by human single-stranded selective monofunctional uracil-DNA glycosylase

hSMUG1 (human single-stranded selective monofunctional uracil-DNA glyscosylase) is one of three glycosylases encoded within a small region of human chromosome 12. Those three glycosylases, UNG (uracil-DNA glycosylase), TDG (thymine-DNA glyscosylase), and hSMUG1, have in common the capacity to remove uracil from DNA. However, these glycosylases also repair other lesions and have distinct substrate preferences, indicating that they have potentially redundant but not overlapping physiological roles. The mechanisms by which these glycosylases locate and selectively remove target lesions are not well understood. In addition to uracil, hSMUG1 has been shown to remove some oxidized pyrimidines, suggesting a role in the repair of DNA oxidation damage. In this paper, we describe experiments in which a series of oligonucleotides containing purine and pyrimidine analogs have been used to probe mechanisms by which hSMUG1 distinguishes potential substrates. Our results indicate that the preference of hSMUG1 for mispaired uracil over uracil paired with adenine is best explained by the reduced stability of a duplex containing a mispair, consistent with previous reports with Escherichia coli mispaired uracil-DNA glycosylase. We have also extended the substrate range of hSMUG1 to include 5-carboxyuracil, the last in the series of damage products from thymine methyl group oxidation. The properties used by hSMUG1 to select damaged pyrimidines include the size and free energy of solvation of the 5-substituent but not electronic inductive properties. The observed distinct mechanisms of base selection demonstrated for members of the uracil glycosylase family help explain how considerable diversity in chemical lesion repair can be achieved

Influence of particle composition and thermal cycling on bijel formation

Colloidal particles with appropriate wetting properties can become very strongly trapped at an interface between two immiscible fluids. We have harnessed this phenomenon to create a new class of soft materials with intriguing and potentially useful characteristics. The material is known as a bijel: bicontinuous interfacially-jammed emulsion gel. It is a colloid-stabilized emulsion with fluid-bicontinuous domains. The potential to create these gels was first predicted using computer simulations. Experimentally we use mixtures of water and 2,6-lutidine at the composition for which the system undergoes a critical demixing transition on warming. Colloidal silica, with appropriate surface chemistry, is dispersed while the system is in the single-fluid phase; the composite sample is then slowly warmed well beyond the critical temperature. The liquids phase separate via spinodal decomposition and the particles become swept up on the newly created interfaces. As the domains coarsen the interfacial area decreases and the particles eventually become jammed together. The resulting structures have a significant yield stress and are stable for many months. Here we begin to explore the complex wetting properties of fluorescently-tagged silica surfaces in water-lutidine mixtures, showing how they can be tuned to allow bijel creation. Additionally we demonstrate how the particle properties change with time while they are immersed in the solvents.Comment: Proceedings of the 7th Liquid Matter Conference, held in Lund (Sweden) in June 200

Hera: evidence for multiple mineralization events and remobilization in a sediment-hosted Au-Pb-Zn-Ag deposit, Central New South Wales, Australia

The Hera Au-Ag-Pb-Zn deposit of central New South Wales, Australia with a total undepleted resource of 3.6 Mt @ 3.3 g/t Au, 25 g/t Ag, 2.6% Pb and 3.8% Zn occurs on the SE margin of the Cobar Basin. It is hosted by the shallow marine Mouramba Group and overlying turbiditic Amphitheatre Group. The siltstones comprise various mixtures of quartz, plagioclase, muscovite-phengite, biotite and clinochlore, along with accessory titanite and ilmenite. The deposit comprises a number of discrete lodes which are steeply west-dipping and strike NNW. Each lode has different abundances of the main ore minerals sphalerite, galena, chalcopyrite, pyrrhotite and electrum-gold. The North Pod and Far West lenses have the most diverse mineralogy in additionally containing arsenopyrite, native silver, gudmundite, Ag-tetrahedrite, acanthite, dyscrasite, native antimony, nisbite and breithauptite. Electrum (continuous spectrum from Ag-rich to Au-rich) is associated with sulfides in the main ore lenses while native gold occurs in the host rocks along cleavages/lineations and away from the main ore. The sulfur isotope data from across the deposit indicates a magmatic source. Most of the deposit has experienced greenschist facies metamorphism with pervasive green chlorite alteration, though the North Pod differs in being distinctly Ag- and Sb-rich and has reached at least amphibolite facies metamorphism with a garnet-wollastonite-vesuvianite-tremolite assemblage. Tremolite is relatively abundant throughout most of the deposit suggesting widespread low-T skarn alteration. Cross-cutting pegmatites comprise quartz, plagioclase (labradorite-andesine) and microcline. Hydrothermal remobilization is relatively extensive and best explains the unusual Ag-Sb-As assemblages of the North Pod and Far West lodes

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

Substrate Entrainment, Depositional Relief, and Sediment Capture: Impact of a Submarine Landslide on Flow Process and Sediment Supply

From Frontiers via Jisc Publications RouterHistory: collection 2021, received 2021-08-12, accepted 2021-10-27, epub 2021-11-16Publication status: PublishedSubmarine landslides can generate complicated patterns of seafloor relief that influence subsequent flow behaviour and sediment dispersal patterns. In subsurface studies, the term mass transport deposits (MTDs) is commonly used and covers a range of processes and resultant deposits. While the large-scale morphology of submarine landslide deposits can be resolved in seismic reflection data, the nature of their upper surface and its impact on both facies distributions and stratal architecture of overlying deposits is rarely resolvable. However, field-based studies often allow a more detailed characterisation of the deposit. The early post-rift Middle Jurassic deep-water succession of the Los Molles Formation is exceptionally well-exposed along a dip-orientated WSW-ENE outcrop belt in the Chacay Melehue depocentre, Neuquén Basin, Argentina. We correlate 27 sedimentary logs constrained by marker beds to document the sedimentology and architecture of a >47 m thick and at least 9.6 km long debrite, which contains two different types of megaclasts. The debrite overlies ramps and steps, indicating erosion and substrate entrainment. Two distinct sandstone-dominated units overlie the debrite. The lower sandstone unit is characterised by: 1) abrupt thickness changes, wedging and progressive rotation of laminae in sandstone beds associated with growth strata; and 2) detached sandstone load balls within the underlying debrite. The combination of these features suggests syn-sedimentary foundering processes due to density instabilities at the top of the fluid-saturated mud-rich debrite. The debrite relief controlled the spatial distribution of foundered sandstones. The upper sandstone unit is characterised by thin-bedded deposits, locally overlain by medium-to thick-bedded lobe axis/off-axis deposits. The thin-beds show local thinning and onlapping onto the debrite, where it develops its highest relief. Facies distributions and stacking patterns record the progradation of submarine lobes and their complex interaction with long-lived debrite-related topography. The emplacement of a kilometre-scale debrite in an otherwise mud-rich basinal setting and accumulation of overlying sand-rich deposits suggests a genetic link between the mass-wasting event and transient coarse clastic sediment supply to an otherwise sand-starved part of the basin. Therefore, submarine landslides demonstrably impact the routing and behaviour of subsequent sediment gravity flows, which must be considered when predicting facies distributions and palaeoenvironments above MTDs in subsurface datasets

“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

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

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