Isolation et caractérisation des cellules souches gingivales (étude de leur potentiel multipotent)

Les capacités de cicatrisation de la gencive en font un modèle de régénération tissulaire naturelle. Ces capacités sont liées en grande partie à l activité des fibroblastes. Composante cellulaire principale du tissu conjonctif gingival, ils sont au cœur de la régulation des réponses inflammatoires et des processus de cicatrisation. Nous avons supposé que ce tissu pouvait contenir des cellules souches, pouvant expliquer en partie, ces capacités de réparation. Au cours de cette thèse, nous avons pu mettre en évidence la présence de cellules souches mésenchymateuses aux propriétés communes avec les cellules souches adultes dérivées des crêtes neurales. Ces cellules expriment des marqueurs spécifiques des cellules souches et des crêtes neurales. Par ailleurs, elles présentent des capacités d auto-renouvellement et de multipotence. Elles sont, en effet, capables de se différencier en adipocytes, ostéocytes et chondrocytes. Nous nous sommes plus particulièrement intéressés à la différenciation chondro/endochondrale. La culture des cellules, sous forme de sphères en suspension, a permis de mettre en évidence leurs capacités de différenciation en tissus cartilagineux et articulaires. Elles s organisent spontanément en plusieurs types cellulaires différents, générant notamment des chondrocytes hypertrophiques et des synoviocytes selon leur localisation au sein des sphères et du milieu de culture utilisé. Le comportement de ces cellules soumises à ces conditions a permis de montrer leurs facultés à reproduire, in vitro, des processus proches de ceux retrouvés au cours du développement. Ces résultats permettent une meilleure compréhension des phénomènes de différenciation des cellules souches adultes, ouvrant ainsi de nouvelles perspectives pour des applications en thérapie cellulaire articulaire et osseuse.The healing capacity of the gingiva makes it a model of natural tissue regeneration. These capabilities are largely related to the fibroblast activity. They are the main cellular component of the gingival connective tissue and they regulate inflammatory responses and healing process. We hypothesized that this tissue could contain stem cells, which could explain, in part, these repair capabilities. In this thesis, we were able to demonstrate the presence of mesenchymal stem cells with properties shared with the neural crest-derived adult stem cells. These cells express specific markers of stem cells and neural crest. Moreover, they do have the capacity to self-renew and multipotency. They are, indeed, able to differentiate into adipocytes, chondrocytes and osteocytes. We have particularly focused on the chondro / endochondral differentiation. When cultivated as micromasses cultures in suspension, cells were able to differentiate into cartilage and joint tissues. They organize themselves spontaneously into several different cell types, including hypertrophic chondrocytes and synoviocytes depending on their location within the micromasses and the culture medium used. The behavior of these cells under these conditions has shown their ability to replicate in vitro, close to those found during the development process. These results allow a better understanding of adult stem cells differentiation, opening new perspectives for applications in joint and bone cell therapy.PARIS5-Bibliotheque electronique (751069902) / SudocSudocFranceF

Crinoids from Svalbard in the aftermath of the end-Permian mass extinction

The end−Permian mass extinction constituted a major event in the history of cri− noids. It led to the demise of the major Paleozoic crinoid groups including cladids, disparids, flexibles and camerates. It is widely accepted that a single lineage, derived from a late Paleo− zoic cladid ancestor (Ampelocrinidae), survived this mass extinction. Holocrinid crinoids (Holocrinus, Holocrinida) along with recently described genus Baudicrinus (Encrinida), the only crinoid groups known from the Early Triassic, are considered the stem groups for the post−Paleozoic monophyletic subclass Articulata. Here, we report preliminary data on unex− pectedly diverse crinoid faunas comprising at least four orders from the Lower Triassic (Induan and Olenekian) of Svalbard, extending their stratigraphic ranges deeper into the early Mesozoic. These findings strongly imply that the recovery of crinoids in the aftermath of the end−Permian extinction began much earlier at higher palaeolatitudes than in the central Tethys

Susceptibility to chronic mucus hypersecretion, a genome wide association study

Background: Chronic mucus hypersecretion (CMH) is associated with an increased frequency of respiratory infections, excess lung function decline, and increased hospitalisation and mortality rates in the general population. It is associated with smoking, but it is unknown why only a minority of smokers develops CMH. A plausible explanation for this phenomenon is a predisposing genetic constitution. Therefore, we performed a genome wide association (GWA) study of CMH in Caucasian populations.Methods: GWA analysis was performed in the NELSON-study using the Illumina 610 array, followed by replication and metaanalysis in 11 additional cohorts. In total 2,704 subjects with, and 7,624 subjects without CMH were included, all current or former heavy smokers (&gt;= 20 pack-years). Additional studies were performed to test the functional relevance of the most significant single nucleotide polymorphism (SNP).Results: A strong association with CMH, consistent across all cohorts, was observed with rs6577641 (p = 4.25610(-6), OR = 1.17), located in intron 9 of the special AT-rich sequence-binding protein 1 locus (SATB1) on chromosome 3. The risk allele (G) was associated with higher mRNA expression of SATB1 (4.3610 29) in lung tissue. Presence of CMH was associated with increased SATB1 mRNA expression in bronchial biopsies from COPD patients. SATB1 expression was induced during differentiation of primary human bronchial epithelial cells in culture.Conclusions: Our findings, that SNP rs6577641 is associated with CMH in multiple cohorts and is a cis-eQTL for SATB1, together with our additional observation that SATB1 expression increases during epithelial differentiation provide suggestive evidence that SATB1 is a gene that affects CMH.</p

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Etude expérimentale et modélisation de la durabilité d'un contact représentatif de l'interface aube / disque de soufflante grenaillé soumis à des chargements de fretting / fatigue / usure

Ce travail porte sur l étude du risque d amorçage de fissure en fretting/fatigue du contact aubes/disque de soufflante en alliage de titane Ti-6Al-4V d un turboréacteur civil. De part les vibrations du moteur et le passage du flux d air, le contact aube/disque est sujet à de microdéplacements: le fretting. Ce problème complexe concerne des zones en contact de faibles dimensions subissant des pressions de contact importantes et des micro-déplacements associées à des structures soumises à des chargements eux-mêmes complexes. Des essais de fretting simple, fretting précontraint et fretting fatigue sont réalisés en vue d identifier les conditions d amorçage de fissure pour plusieurs géométries présentant des gradients de contraintes différents. Les résultats expérimentaux mettent en évidence l effet du gradient de contrainte sur l amorçage. Ainsi, via des essais présentant une gamme étendue de gradient, il a été confirmé que les gradients de contraintes retardent l initiation de fissure. Une approche non-locale couplée à un critère de fatigue multiaxiale et identifiée sur une unique condition expérimentale de fretting simple a permis la prédiction de l ensemble des résultats expérimentaux. Ainsi, une méthodologie prédictive des durées de vie à amorçage a été proposée. Cette approche numérique intègre la multiaxialité du chargement, l effet du gradient des contraintes, la réponse élastoplastique de l interface et les limites de fatigue en traction/compression et torsion alternée du matériau. L interface aube/disque grenaillée du moteur subit une alternance de sollicitations de faibles amplitudes générant l amorçage de fissure, et de grandes amplitudes favorisant l usure des zones en contact. Le phénomène de compétition usure/fissure a alors été étudié via les courbes en cloches (durée de vie en fonction de l amplitude de déplacement) ainsi que l influence des contraintes résiduelles de grenaillage. Une première conclusion sur l effet bénéfique de l usure a pu être apportée dans le cas d un matériau sans traitement de surface. Si les contraintes résiduelles de grenaillage permettent d apporter un gain notable sur les durées de vie pour des sollicitations de glissement partiel, à l inverse, il a été observé que le matériau avec le traitement de surface de grenaillage présente des durées de vie plus faibles pour des sollicitations favorisant l usure. À travers d essais inédits avec un dispositif expérimental à trois vérins, le chargement complexe de l interface aube/disque du moteur a pu être reproduit à l échelle du laboratoire. Ainsi, la durabilité globale du contact représentatif de l interface aube/disque de soufflante a été étudiée. Une synergie des sollicitations oligocycliques et polycycliques à l interface a été constatée provoquant des phénomènes de réorganisation de contraintes résiduelles et l accélération des cinétiques d usure. Cette étude a montré l importance de prendre en compte les sollicitations polycycliques dans le dimensionnement des structures aubes/disque. Ces sollicitations couplent les aspects de fatigue fissuration aux phénomènes de cumul de dommage et de cinétique d usure des interfaces.This work aims at studying the crack initiation risk of a blade/disk contact under fretting/fatigue loading. The fan stage of a civil engine is studied and the material used is a titanium alloy: Ti-6Al-4V. This complex issue concerns small contacts which are subjected to high contact pressures and micro-displacements. Thus, a complex multiaxial loading occurs on the structure. Fretting, static stressed fretting and fretting fatigue testing are performed in order to quantify the crack nucleation thresholds. In addition, several geometries which present different stress gradient values are used. The experimental results show a stress gradient effect on the crack initiation. Thus, using a wide range of stress gradient, it has been confirmed that stress gradient delays crack nucleation. A multiaxial fatigue criterion is used to determine the equivalent stress field under the contact. Then, a non-local approach, identified thanks to one fretting experimental condition, is employed in order to consider the stress gradient effect. This approach provides the prediction of the whole experimental results. In this way, a predictive method of the initiation fatigue life has been introduced. This numerical approach takes into account the multiaxial loading, the stress gradient effect, the plastic-elastic behavior of the interface and the fatigue strength limits of the material. The blade/disk contacts of the engine are shot-peened. During the flight, interfaces are subjected to low displacement amplitudes leading to crack initiation. On the other hand, during landing and take-off, contacts are submitted to high displacement amplitudes leading to the interface wear. As a consequence, competition between wear kinetic and nucleation one is studied and bell curves are plotted (i.e. fatigue life time versus displacement amplitude).Moreover, the effect of the shot-peening residual stresses on fatigue life time is observed. In case of un-treated material, a beneficial impact on the fatigue life time is observed due to wear process. Compressive residual stresses of shot-peening increase the fatigue life when fretting/fatigue on partial slip regime occurs. Nevertheless, a decrease of the fatigue life time is observed when wear process is activated by the gross slip condition. Finally, the complex loading of the engine blade/disk contact has been reproduced in the laboratory. To achieve this, a new testing, using an experimental machine composed of three hydraulic actuators is developed. Thus, the global life time of the representative interface of the fan stage is studied. Oligocyclic (low frequency) and polycyclic (high frequency) solicitations interact themselves and lead, firstly, to a rearrangement of the residual stresses, and secondly, to an increase of the wear kinetics. This research work highlights the interest to consider the polycyclic loadings to design the blade/disk structure. These solicitations reproduce the cracking fatigue phenomenon, the cumulative damages and the wear kinetics of the interface.LYON-Ecole Centrale (690812301) / SudocSudocFranceF

Roveacrinid microfacial assemblages (Roveacrinida, Crinoidea) from the Lower-Middle Cenomanian of the Adyaman area (SE Turkey)

In the northwestern part of the Arabian Platform, the Adyaman district (SE Turkey) displays some Lower-Middle Cenomanian deep-marine sediments of the Derdere Formation. These sediments are yielding abundant echinodermal remains, among which some thecal and brachial plates are assignable to roveacrinids. Routine microfacies analysis of the Lower-Middle Cenomanian part of the Derdere Formation revealed unexpected early Cenomanian assemblages of roveacrinoidal ossicles, comparable with those formerly reported further south in the Cenomanian-Turonian of the Arabian Platform. For the first time, genuine and undisputable Roveacrinidae are illustrated for SE Turkey. Seven borehole sections were scrutinized in search of microcrinoidal sections, most especially within carbonate microfacies. Within the scope of better constraining the position of the Lower-Middle Cenomanian, we had been compiling the successive occurrence of respective identified roveacrinid remains. These roveacrinidal assemblages are consisting in: Roveacrinus communis Douglas (1908) (= R. derdereensis Farinacci & Manni); Roveacrinus cf. alatus Douglas (1908); Roveacrinus spinosus Peck (1943); Roveacrinus sp.; Roveacrinidae indet.; Applinocrinus sp.; and Saccocomidae indet. These specimens provide significant clues to constrain the palaeogeographic reconstruction of Tethyan seaways, and represent potential fossil index candidates for the Lower Cenomanian stratigraphy of the Adyaman district

AFCP French Total Ankle Replacement Registry

Category: Ankle Arthritis Introduction/Purpose: In 2015-2016, renewal of the 5-yearly French health insurance financing of TAR requires exhaustive data. The French Foot Surgery Society (AFCP – project initiator and promoter), Lyon University Hospitals Clinical Research Unit (administrator and scientific manager) and manufacturers (operational financers) therefore launched a national TAR registry on June 18, 2012 (CNIL data protection approval). For each TAR, there are 3 forms: prosthesis patient data, reoperation, monitoring (optional).We present results for the first 3 years. Methods: Under the 3-party contract, manufacturers pay for 6-monthly reports and €32 per prosthesis to cover the reminder procedure (each company gives the Research Unit a monthly list of surgeons, and the Unit sends out 3 reminders to those who have not entered data). Every surgeon implanting TARs must file a pre-registration formula on the website; after verification, the administrator sends the center number and personal login. Registration takes 3-5 minutes; implant ID number is automatically provided after complete data input. Then surgeons distribute a legal information sheet plus passport (patients can alert the research unit directly in case of re-operation). From June 2012 to June 2015, 1276 of the 1,612TARs implanted in France were registered (79.2%): 514 Salto, 353 SaltoTalaris, 307 Hintegra, 81 Star, 21 Akile. 202 centers implanted TARs: 127 registered TARs in the Registry, 75 registered none. Ten centers registered more than 30 (737 TARs), and 36 only one; surgeon investment was proportional to number of TARs (41% registration rate in centers registering one TAR to 94% in centers registering more than 10 TARs). Results: Mean age at implantation was 63.4 years (18-91 years); etiology was mainly post-traumatic (49%), osteoarthritis on laxity (19%), primary (17%) or inflammatory (7%), with some hindfoot misalignment (21% varus >5°, 11% valgus >5°). Surgery comprised: 97% standard implants (MB thickness mainly 4 mm (26%) or 5 mm (25%)); tourniquet time, 89 min; malleolar fracture, 6.4%; associated Achilles lengthening, 20.9%; ligament plasty, 8.6%; osteotomy, 4.9%; arthrodesis, 2.3%. 528 patients (41.4%) had at least 1 follow-up form (wound healing delay 6.8%, infection 0.7%, DF 9.9°, PF 22.1°). At 3 years, 74 patients (5.8%) were reoperated on (17 patients (2%) at 2 yrs): i.e. 89 reoperations (1-4/patient). 51 patients (4%) had revision without implant removal (arthrolysis 33%, complementary osteotomy 11.5%, Achilles lengthening 9.8%, ligament plasty 6.6%, etc); 9 (0.7%) with partial TAR change (tibia 6 – talus 3); 14 (1.1%) with TAR removal (4 re-do TAR, 8 arthrodesis, 2 temporary spacer before arthrodesis). Conclusion: Follow-up was insufficient to assess survival. This registry procedure, closely followed by the health authorities, has overcome French surgeons’ aversion for registries (exhaustiveness 2% for French Hip registry). Exhaustiveness could be improved if taken into account for surgeons’ accreditation. But an independent annual telephone audit requested by HAS (French Health Authority) showed that at 1 year the registry detected only 29% of reoperations vs phone call survey of registry patients: registries are not the gold standard and probably overestimate the real survival rate

Frequency Identification of a Memory Polynomial Model for PA Modeling

Abstract—In this paper, we describe the validation of the modeling of a power amplifier. The model used is a memory polynomial model. We propose a method of identification in the frequency domain, from characteristic points (in amplitude and in phase) which are the fundamental and the inter-modulation tones. We then describe the realization of a test-bench suitable for the validation of this model

Assessment of standard coil positioning in transcranial magnetic stimulation in depression

International audienceTranscranial magnetic stimulation (TMS) is a non-invasive technique used in the treatment of major depression. Meta-analyses have shown that it is more efficient than a placebo and that its efficacy is enhanced by the optimum tuning of stimulation parameters. However, the stimulation target, the dorsolateral prefrontal cortex (DLPFC), is still located using an inaccurate method. In this study, a neuronavigation system was used to perform a comprehensive quantification of target localization errors. We identified and quantified 3 sources of error in the standard method: cap repositioning, interexpert variability in coil positioning and distance between the stimulated point and the expected target. For cap repositioning, the standard deviation was lower than 5 mm in the 3 axes. For interexpert variability in coil positioning, the spatial dispersion of the points was higher than 10 mm in 2 of the 3 axes. For interindividual anatomical variability, the distance between the actual “reference” DLPFC and its standard determination was greater than 20 mm for 54% of the subjects, while one subject out of eleven was correctly targeted which means 10 mm or less from the reference. Results showed that interindividual anatomical variability and interexpert variability were the two main sources of error using the standard method. Results demonstrate that a neuronavigation system is mandatory to conduct reproducible and reliable studies

Copper Complexes as Bioinspired Models for Lytic Polysaccharide Monooxygenases

International audienceWe report here two copper complexes as first functional models for lytic polysaccharide monooxygenases, mononuclear copper-containing enzymes involved in recalcitrant polysaccharide breakdown. These complexes feature structural and spectroscopic properties similar to those of the enzyme. In addition, they catalyze oxidative cleavage of the model substrate p-nitrophenyl-β-d-glucopyranoside. More importantly, a particularly stable copper(II) hydroperoxide intermediate is detected in the reaction condition