15 resultados para Anchors.

em Université de Lausanne, Switzerland


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We demonstrate that the cccB gene, identified in the Bacillus subtilis genome sequence project, is the structural gene for a 10-kDa membrane-bound cytochrome c(551) lipoprotein described for the first time in B. subtilis. Apparently, CccB corresponds to cytochrome c(551) of the thermophilic bacterium Bacillus PS3. The heme domain of B. subtilis cytochrome c(551) is very similar to that of cytochrome c(550), a protein encoded by the cccA gene and anchored to the membrane by a single transmembrane polypeptide segment. Thus, B. subtilis contains two small, very similar, c-type cytochromes with different types of membrane anchors. The cccB gene is cotranscribed with the yvjA gene, and transcription is repressed by glucose. Mutants deleted for cccB or yvjA-cccB show no apparent growth, sporulation, or germination defect. YvjA is not required for the synthesis of cytochrome c(551), and its function remains unknown.

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In response to stress, the heart undergoes a pathological remodeling process associated with hypertrophy and the reexpression of a fetal gene program that ultimately causes cardiac dysfunction and heart failure. In this study, we show that A-kinase-anchoring protein (AKAP)-Lbc and the inhibitor of NF-κB kinase subunit β (IKKβ) form a transduction complex in cardiomyocytes that controls the production of proinflammatory cytokines mediating cardiomyocyte hypertrophy. In particular, we can show that activation of IKKβ within the AKAP-Lbc complex promotes NF-κB-dependent production of interleukin-6 (IL-6), which in turn enhances fetal gene expression and cardiomyocyte growth. These findings provide a new mechanistic hypothesis explaining how hypertrophic signals are coordinated and conveyed to interleukin-mediated transcriptional reprogramming events in cardiomyocytes.

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The mitogen-activated protein kinases (MAPKs) pathways are highly organized signaling systems that transduce extracellular signals into a variety of intracellular responses. In this context, it is currently poorly understood how kinases constituting these signaling cascades are assembled and activated in response to receptor stimulation to generate specific cellular responses. Here, we show that AKAP-Lbc, an A-kinase anchoring protein (AKAP) with an intrinsic Rho-specific guanine nucleotide exchange factor activity, is critically involved in the activation of the p38α MAPK downstream of α(1b)-adrenergic receptors (α(1b)-ARs). Our results indicate that AKAP-Lbc can assemble a novel transduction complex containing the RhoA effector PKNα, MLTK, MKK3, and p38α, which integrates signals from α(1b)-ARs to promote RhoA-dependent activation of p38α. In particular, silencing of AKAP-Lbc expression or disrupting the formation of the AKAP-Lbc·p38α signaling complex specifically reduces α(1)-AR-mediated p38α activation without affecting receptor-mediated activation of other MAPK pathways. These findings provide a novel mechanistic hypothesis explaining how assembly of macromolecular complexes can specify MAPK signaling downstream of α(1)-ARs.

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Introduction: Absorbable anchors are frequently used in shoulder surgery. Mechanisms of absorption induce a local inflammatory reaction. It is not clear if this process may disturb healing of the capsule and ligaments. The purpose of the study was to compare the rate of recurrent dislocation following open shoulder stabilization when using absorbable or non-absorbable suture anchors. Methods: Between 1999 and 2003, 83 open Bankart repairs were performed by the same surgeon. All patients had recurrent traumatic anterior shoulder instability. All had preoperative arthro-MRI or arthro-CT which did not reveal any significant bony Bankart lesion or rotatorcuff tear. Thirty-four patients were treated with absorbable anchors (Panalok®) and sutures (Panacryl®) and 49 with non-absorbable anchors (Mitek GII®) and sutures (Ethibond®). The same surgical technique and rehabilitation protocol were used. The incidence of sports ability and recurrent instability were recorded. We defined instability as true dislocation. Results: Five patients on 34 were lost to follow-up in the absorbable group and 7 on 49 in the non-absorbable group. The mean age of absorbable group was 25 years (range, 17-39 years). At a mean follow-up of 66 months (range, 54-76 months), 86% could resume sports activity. Five patients on 29 (17%) reported recurrent instability and two did need revision surgery. The mean age in non-absorbable group was 28 year (range, 18-47 years). At a mean follow-up of 78 months (range, 49-82 months), 93% could resume sports activity. Three patients on 42 (7%) reported recurrent instability and one did need revision surgery. Conclusion: This clinical study showed a clear tendency to a higher recurrence rate of dislocation when using absorbable suture anchors (17% in absorbable vs 7% in non-absorbable group). It is known that Panacryl® may be responsible for a major local inflammatory response. However, it is still unclear if this could be the failure etiology. Consequently, we prefer to use systematically non-absorbable sutureanchors for shoulder stabilization.

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Membrane fusion is induced by SNARE complexes that are anchored in both fusion partners. SNAREs zipper up from the N to C terminus bringing the two membranes into close apposition. Their transmembrane domains (TMDs) might be mere anchoring devices, deforming bilayers by mechanical force. Structural studies suggested that TMDs might also perturb lipid structure by undergoing conformational transitions or by zipping up into the bilayer. Here, we tested this latter hypothesis, which predicts that the activity of SNAREs should depend on the primary sequence of their TMDs. We replaced the TMDs of all vacuolar SNAREs (Nyv1, Vam3, and Vti1) by a lipid anchor, by a TMD from a protein unrelated to the membrane fusion machinery, or by artificial leucine-valine sequences. Individual exchange of the native SNARE TMDs against an unrelated transmembrane anchor or an artificial leucine-valine sequence yielded normal fusion activities. Fusion activity was also preserved upon pairwise exchange of the TMDs against unrelated peptides, which eliminates the possibility for specific TMD-TMD interactions. Thus, a specific primary sequence or zippering beyond the SNARE domains is not a prerequisite for fusion. Lipid-anchored Vti1 was fully active, and lipid-anchored Nyv1 permitted the reaction to proceed up to hemifusion, and lipid-anchored Vam3 interfered already before hemifusion. The unequal contribution of proteinaceous TMDs on Vam3 and Nyv1 suggests that Q- and R-SNAREs might make different contributions to the hemifusion intermediate and the opening of the fusion pore. Furthermore, our data support the view that SNARE TMDs serve as nonspecific membrane anchors in vacuole fusion.

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Objective: The aim of this study was to determine the smallest changes in health-related quality of life (HRQOL) scores in the European Organization for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ-C30) and the EORTC Brain Cancer Module (QLQ-BN20), which could be considered as clinically meaningful in brain cancer patients. Methods: World Health Organization (WHO) performance status (PS) and the Mini Mental State Examination (MMSE) were used as clinical anchors to determine minimal clinically important differences (MCID) in HRQOL change scores (range 0 - 100) in the EORTC QLQ-C30 and QLQ-BN20. Anchor-based MCID estimates less than 0.2SD (small effect) were not recommended for interpretation. Other selected distribution-based methods were also used for comparison purposes. Results: Based on WHO PS, our findings support the following whole number estimates of the MCID for improvement and deterioration respectively: physical functioning (6, 9), role functioning (14, 12), cognitive functioning (8, 8), global health status (7, 4*), fatigue (12, 9) and motor dysfunction (4*, 5). Anchoring with MMSE, cognitive functioning MCID estimates for improvement and deterioration were (11, 2*) and those for communication deficit were (9, 7). The estimates with asterisks were less that the set 0.2 SD threshold and are therefore not recommended for interpretation. Our MCID estimates therefore range from 5-14. Conclusion: These estimates can help clinicians to evaluate changes in HRQOL over time and, in conjunction with other measures of efficacy, help to assess the value of a health care intervention or to compare treatments. Furthermore, the estimates can be useful in determining sample sizes in the design of future clinical trials.

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Résumé : Au cours de l'évolution, les organismes multicellulaires ont développé le système immunitaire afin de pouvoir se défendre contre les pathogènes tel que les bactéries, les virus, et les parasites. La réponse immunitaire doit être finement régulée par différentes voies de signalisation moléculaire, afin d'assurer une efficacité optimale, et d'éviter des dommages tissulaires indésirables. Les résultats expérimentaux décrits dans ce manuscrit, mettent en évidence que la protéine Unc5CL, qui contient un death domain (DD), est impliquée dans la régulation de la réponse immunitaire des muqueuses. Il a été démontré que cette protéine contient aussi un domaine transmembranaire de type III dans sa partie N-terminale, permettant ainsi de l'ancrer et d'exposer sa partie C-terminale dans le cytosol, un prérequis pour la signalisation dans ce compartiment cellulaire. De plus, cette protéine a la capacité d'activer le facteur de transcription NFxB, qui joue un rôle important dans le système immunitaire, ainsi que dans d'autres processus cellulaires essentiels. Le profil transcriptionnel révèle que l'activation de NF-κB induite par Unc5CL conduit principalement à une réponse inflammatoire, qui se caractérise par la production de diverses chimiokines (e.g. CXCL-1, IL-8 et CCL20). Il a également été démontré que Unc5CL requiert les mêmes molécules qui sont utilisées dans la voie de signalisation des récepteurs de la famille toll et de l'interleukine-1. De manière similaire à leur protéine adaptatrice MyD88, Unc5CL a la capacité de recruter, via une interaction homotypique DD-DD, les kinases IRAK1 et IRAK4 qui contiennent elles aussi un DD, permettant ainsi au signal d'être transmis. La production d'un anticorps polyclonal contre le DD de Unc5CL a permis d'identifier des lignées cellulaires et des tissus exprimant cette protéine, ainsi que de déterminer sa localisation sub-cellulaire. Unc5CL a été détecté dans les cellules de la muqueuse utérine et intestinale, ainsi que dans une lignée cellulaire issue d'un adénocarcinome colorectal humain, les CaCo-2. Dans chacun de ces cas, Unc5CL a été principalement détectée au niveau apical des cellules épithéliales polarisées. De manière similaire à PIDD, une protéine impliquée dans la réponse aux dommages à l'ADN, et au constituant des pores nucléaires Nup98, Unc5CL est constitutivement clivé de manière autoprotéolytique, au niveau d'un site HFS. Il est intéressant d'observer que les deux fragments ainsi générés restent fortement associés l'un à l'autre après clivage. Finalement, un criblage protéomique pour identifier un partenaire d'interaction, a mis en évidence l'ubiquitin ligase E3 ITCH, qui régule de manière négative Unc5CL en augmentant sa dégradation. Summary : Multicellular organisms have evolved the immune system in order to defend themselves against pathogens such as bacteria, viruses and eukaryotic parasites. Immune responses have to be tightly orchestrated by signaling mechanisms to achieve optimal effectiveness and minimal tissue damage. The experimental results in this thesis manuscript provide evidence that the death domain (DD)-containing protein Unc5CL might be involved in the regulation of mucosal immune responses. It could be shown that the protein contains an N-terminal type-III transmembrane domain that anchors the protein with its C-terminus exposed to the cytosol, a prerequisite for signaling events in this compartment. Furthermore, the protein has the capacity to activate the transcription factor NF-κB, which plays an important role in the immune system as well as in other essential cellular processes. Transcriptional profiling revealed that Unc5CL-mediated activation of NF-κB mainly leads to an inflammatory response, characterized by the production of chemokines (e.g. CXCL-l, IL-8 and CCL20). Furthermore, it could be shown that Unc5CL requires the same downstream signaling molecules as the evolutionarily ancient tolUinterleukin-1 receptor family. Similar to their adapter protein MyD88, Unc5CL has the capacity to recruit the DD-containing kinases IRAKI and IRAK4 for signaling and can interact with these proteins via homotypic DD-DD interactions. Generation of polyclonal antibodies raised against the DD of Unc5CL allowed the identification of cell lines and tissues that express the endogenous protein as well as to confine its subcellular localization. Unc5CL was detected in primary mucosal uterine and intestinal epithelial cells as well as in the human colorectal adenocarcinoma cell line CaCo-2. In all cases, the protein was mainly localized to the apical face of these polarized epithelial cells. Similar to PIDD, a protein critically involved in responses to DNA damage, and the nuclear pore component Nup98, Unc5CL is constitutively autoproteolytically processed at an HFS site. Interestingly, the two generated cleavage fragments remain tightly associated after processing. Finally, a proteomics screen for interaction partners identified the E3 ubiquitin ligase ITCH as a negative regulator of Unc5CL by targeting the protein for degradation.

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BACKGROUND: Chronic lateral ankle instability accounts for 20% of the ankle injuries. This study evaluates functional outcome of the modified Broström-Gould technique using suture anchors, with 4 different clinical scores. METHODS: A consecutive series of 41 patients were included with a minimum follow-up of one year. The function was assessed using 4 clinical scores including: the AOFAS for hind foot; the FAAM; the CAIT and the CAIS. RESULTS: Out of 41 patients; 27 patients were very satisfied, 11 satisfied and 3 were not satisfied. Ankle mobility returned to normal in 93% of patients. At follow-up the AOFAS was 89/100 (37-100), the FAAM 85/100% (35-100%), the CAIT 20/30 (5-30), and the CAIS 74/100% (27-100%). CONCLUSION: Outcome of modified Broström-Gould procedure is good with high satisfaction rate in terms of ankle mobility. The disparity in outcome of scores, signals towards the need of a standard evaluation system.

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The purpose of this study was to evaluate the results of an anatomic open stabilization procedure. Twenty-three consecutive patients with traumatic, recurrent, anterior glenohumeral instability were managed with a modified open procedure. All had a Bankart lesion. A standardized, true anatomic capsulolabral reconstruction was performed with suture anchors. Two patients were lost to follow-up, and twenty-one were evaluated after 36 months [range, 24-49 months] by an independent observer. Shoulder stability and function were the principal outcome measures. None of the patients had subsequent dislocations. All returned to full working capacity, and 19 reached their previous level of sport activities. The mean loss in active abduction and flexion was 1 degrees, in internal rotation, one vertebral level, and in external rotation, 7 degrees (arm at 90 degrees of abduction). Two patients had a positive anterior apprehension test. No sign of shoulder osteoarthritis was observed. The open anatomic capsulolabral reconstruction provides excellent results and allows the restoration of stability with good function.

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BACKGROUND: We aimed to determine the smallest changes in health-related quality of life (HRQoL) scores in the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire core 30 and the Brain Cancer Module (QLQ-BN20), which could be considered as clinically meaningful in brain cancer patients. Materials and methods: World Health Organisation performance status (PS) and mini-mental state examination (MMSE) were used as clinical anchors appropriate to related subscales to determine the minimal clinically important differences (MCIDs) in HRQoL change scores (range 0-100) in the QLQ-C30 and QLQ-BN20. A threshold of 0.2 standard deviation (SD) (small effect) was used to exclude anchor-based MCID estimates considered too small to inform interpretation. RESULTS: Based on PS, our findings support the following integer estimates of the MCID for improvement and deterioration, respectively: physical (6, 9), role (14, 12), and cognitive functioning (8, 8); global health status (7, 4*), fatigue (12, 9), and motor dysfunction (4*, 5). Anchoring with MMSE, cognitive functioning MCID estimates for improvement and deterioration were (11, 2*) and for communication deficit were (9, 7). Estimates with asterisks were <0.2 SD and were excluded from our MCID range of 5-14. CONCLUSION: These estimates can help clinicians evaluate changes in HRQoL over time, assess the value of a health care intervention and can be useful in determining sample sizes in designing future clinical trials.

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The success of anatomic repair of Bankart lesion diminishes in the presence of a capsule stretching and/or attenuation is reported in a variable percentage of patients with a chronic gleno-humeral instability. We introduce a new arthroscopic stitch, the MIBA stitch, designed with a twofold aim: to improve tissue grip to reduce the risk of soft tissue tear, particularly cutting through capsular-labral tissue, to and address capsule-labral detachment and capsular attenuation using a double loaded suture anchor. This stitch is a combination of horizontal mattress stitch passing through the capsular-labral complex in a "south-to-north" direction and an overlapping single vertical suture passing through the capsule and labrum in a "east-to-west" direction. The mattress stitch is tied before the vertical stitch in order to reinforce the simple vertical stitch, improving grip and contact force between capsular-labral tissue and glenoid bone.

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Partial trapeziectomy with suspension ligamentoplasty is a commonly performed treatment of thumb osteoarthritis. Nevertheless, the post-operative recovery remains long and critical reason for which different modifications of the surgical technique have been proposed. To compare two suspension ligamentoplasty techniques, one with a mitek anchor and another without, a retrospective study of 55 consecutive operated patients was performed. A detailed clinical analysis of pain, function and a radiologic assessment of the trapeziometacarpal space were performed. Mitek anchor fixation was associated with a shorter convalescence period. However, in spite of an improved radiological maintenance of the scaphometacarpal space, mitek anchor fixation was associated with an impaired postoperative function and residual pain when compared with the conventional suspension ligamentoplasty procedure. Patient's satisfaction was comparable in both groups. In our series stabilization of the suspension ligamentoplasty procedure by the insertion of a mitek anchor did not bring the hoped benefits to the patients with a trapeziometacarpal arthritis.

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We examined the moderating role of national identification in understanding when a focus on intergroup similarity versus difference on ingroup stereotypical traits-manipulated with scale anchors-leads to support for discriminatory immigration policies. In line with intergroup distinctiveness research, national identification moderated the similarity-difference manipulation effect. Low national identifiers supported discriminatory immigration policies more when intergroup difference rather than similarity was made salient, whereas the opposite pattern was found for high national identifiers: They trended toward being more discriminatory when similarity was made salient. The impact of assimilation expectations and national identity content on the findings is discussed.

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Introduction: Ankle sprains affect 200'000 persons/year in Switzerland. Most incidences are successfully treated by conservative measures but 20% require reconstruction for symptomatic chronic lateral ankle instability. This study evaluates the functional outcome after a modified Broström-Gould technique as measured by different clinical scores and compares the functional outcome of this technique with other surgical treatments of ankle instability. Methods: This retrospective cohort study evaluates 47 patients who underwent a modified Broström-Gould procedure using suture anchors to refix the lateral ankle capsuloligamentary structures at our institution from 2005 to 2009 with a minimum follow-up of one year (13-72 Mo). All patients were operated by one single surgeon and evaluated by an independent examiner. The function was assessed using 4 scores including: the AOFAS (American Orthopaedic Foot and Ankle Society's Score) hindfoot score; the FAAM (Foot and Ankle Ability Measurement); the CAIT (Cumberland Ankle Instability Tool); the CAIS (Chronic Ankle Instability Scale). Results: Six patients were excluded leaving 41 patients for examination. 34 patients (83%) thought that their ankle was more stable after the surgery, 7 (17%) did not feel any difference. 27 patients were very satisfied, 11 satisfied and 3 not satisfied. Reasons for non satisfaction included persistent instability and pain. Ankle mobility returned to normal in 93% of patients. Five patients had transcient hypoesthesy in the area of the superficial peroneal nerve. One patient suffered from a superficial infection treated successfully by local measures. 80% had the perception of a normal ankle, 20% thought to be below normal. At follow-up the AOFAS was 89/100 (37-100), the FAAM 85/100% (35-100%), the CAIT 20/30 (5-30), and the CAIS 74/100% (27-100%). Conclusions: The modified Broström-Gould procedure, which belongs to the anatomic ankle stabilizations is relatively simple and offers good outcome that satisfied 93% of the patients in the present study. No active stabilisator is sacrificed. Preservation of the ankle mobility is better and the complication rate is lower than after non-anatomical procedures described in the literature. The CAIT appeared as the most severe score compared to the other scales used in our study.

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Les reconstructions palinspastiques fournissent le cadre idéal à de nombreuses études géologiques, géographiques, océanographique ou climatiques. En tant qu?historiens de la terre, les "reconstructeurs" essayent d?en déchiffrer le passé. Depuis qu?ils savent que les continents bougent, les géologues essayent de retracer leur évolution à travers les âges. Si l?idée originale de Wegener était révolutionnaire au début du siècle passé, nous savons depuis le début des années « soixante » que les continents ne "dérivent" pas sans but au milieu des océans mais sont inclus dans un sur-ensemble associant croûte « continentale » et « océanique »: les plaques tectoniques. Malheureusement, pour des raisons historiques aussi bien que techniques, cette idée ne reçoit toujours pas l'écho suffisant parmi la communauté des reconstructeurs. Néanmoins, nous sommes intimement convaincus qu?en appliquant certaines méthodes et certains principes il est possible d?échapper à l?approche "Wégenerienne" traditionnelle pour enfin tendre vers la tectonique des plaques. Le but principal du présent travail est d?exposer, avec tous les détails nécessaires, nos outils et méthodes. Partant des données paléomagnétiques et paléogéographiques classiquement utilisées pour les reconstructions, nous avons développé une nouvelle méthodologie replaçant les plaques tectoniques et leur cinématique au coeur du problème. En utilisant des assemblages continentaux (aussi appelés "assemblées clés") comme des points d?ancrage répartis sur toute la durée de notre étude (allant de l?Eocène jusqu?au Cambrien), nous développons des scénarios géodynamiques permettant de passer de l?une à l?autre en allant du passé vers le présent. Entre deux étapes, les plaques lithosphériques sont peu à peu reconstruites en additionnant/ supprimant les matériels océaniques (symbolisés par des isochrones synthétiques) aux continents. Excepté lors des collisions, les plaques sont bougées comme des entités propres et rigides. A travers les âges, les seuls éléments évoluant sont les limites de plaques. Elles sont préservées aux cours du temps et suivent une évolution géodynamique consistante tout en formant toujours un réseau interconnecté à travers l?espace. Cette approche appelée "limites de plaques dynamiques" intègre de multiples facteurs parmi lesquels la flottabilité des plaques, les taux d'accrétions aux rides, les courbes de subsidence, les données stratigraphiques et paléobiogéographiques aussi bien que les évènements tectoniques et magmatiques majeurs. Cette méthode offre ainsi un bon contrôle sur la cinématique des plaques et fournit de sévères contraintes au modèle. Cette approche "multi-source" nécessite une organisation et une gestion des données efficaces. Avant le début de cette étude, les masses de données nécessaires était devenues un obstacle difficilement surmontable. Les SIG (Systèmes d?Information Géographiques) et les géo-databases sont des outils informatiques spécialement dédiés à la gestion, au stockage et à l?analyse des données spatialement référencées et de leurs attributs. Grâce au développement dans ArcGIS de la base de données PaleoDyn nous avons pu convertir cette masse de données discontinues en informations géodynamiques précieuses et facilement accessibles pour la création des reconstructions. Dans le même temps, grâce à des outils spécialement développés, nous avons, tout à la fois, facilité le travail de reconstruction (tâches automatisées) et amélioré le modèle en développant fortement le contrôle cinématique par la création de modèles de vitesses des plaques. Sur la base des 340 terranes nouvellement définis, nous avons ainsi développé un set de 35 reconstructions auxquelles est toujours associé un modèle de vitesse. Grâce à cet ensemble de données unique, nous pouvons maintenant aborder des problématiques majeurs de la géologie moderne telles que l?étude des variations du niveau marin et des changements climatiques. Nous avons commencé par aborder un autre problème majeur (et non définitivement élucidé!) de la tectonique moderne: les mécanismes contrôlant les mouvements des plaques. Nous avons pu observer que, tout au long de l?histoire de la terre, les pôles de rotation des plaques (décrivant les mouvements des plaques à la surface de la terre) tendent à se répartir le long d'une bande allant du Pacifique Nord au Nord de l'Amérique du Sud, l'Atlantique Central, l'Afrique du Nord, l'Asie Centrale jusqu'au Japon. Fondamentalement, cette répartition signifie que les plaques ont tendance à fuir ce plan médian. En l'absence d'un biais méthodologique que nous n'aurions pas identifié, nous avons interprété ce phénomène comme reflétant l'influence séculaire de la Lune sur le mouvement des plaques. La Lune sur le mouvement des plaques. Le domaine océanique est la clé de voute de notre modèle. Nous avons attaché un intérêt tout particulier à le reconstruire avec beaucoup de détails. Dans ce modèle, la croûte océanique est préservée d?une reconstruction à l?autre. Le matériel crustal y est symbolisé sous la forme d?isochrones synthétiques dont nous connaissons les âges. Nous avons également reconstruit les marges (actives ou passives), les rides médio-océaniques et les subductions intra-océaniques. En utilisant ce set de données très détaillé, nous avons pu développer des modèles bathymétriques 3-D unique offrant une précision bien supérieure aux précédents.<br/><br/>Palinspastic reconstructions offer an ideal framework for geological, geographical, oceanographic and climatology studies. As historians of the Earth, "reconstructers" try to decipher the past. Since they know that continents are moving, geologists a trying to retrieve the continents distributions through ages. If Wegener?s view of continent motions was revolutionary at the beginning of the 20th century, we know, since the Early 1960?s that continents are not drifting without goal in the oceanic realm but are included in a larger set including, all at once, the oceanic and the continental crust: the tectonic plates. Unfortunately, mainly due to technical and historical issues, this idea seems not to receive a sufficient echo among our particularly concerned community. However, we are intimately convinced that, by applying specific methods and principles we can escape the traditional "Wegenerian" point of view to, at last, reach real plate tectonics. This is the main aim of this study to defend this point of view by exposing, with all necessary details, our methods and tools. Starting with the paleomagnetic and paleogeographic data classically used in reconstruction studies, we developed a modern methodology placing the plates and their kinematics at the centre of the issue. Using assemblies of continents (referred as "key assemblies") as anchors distributed all along the scope of our study (ranging from Eocene time to Cambrian time) we develop geodynamic scenarios leading from one to the next, from the past to the present. In between, lithospheric plates are progressively reconstructed by adding/removing oceanic material (symbolized by synthetic isochrones) to major continents. Except during collisions, plates are moved as single rigid entities. The only evolving elements are the plate boundaries which are preserved and follow a consistent geodynamical evolution through time and form an interconnected network through space. This "dynamic plate boundaries" approach integrates plate buoyancy factors, oceans spreading rates, subsidence patterns, stratigraphic and paleobiogeographic data, as well as major tectonic and magmatic events. It offers a good control on plate kinematics and provides severe constraints for the model. This multi-sources approach requires an efficient data management. Prior to this study, the critical mass of necessary data became a sorely surmountable obstacle. GIS and geodatabases are modern informatics tools of specifically devoted to store, analyze and manage data and associated attributes spatially referenced on the Earth. By developing the PaleoDyn database in ArcGIS software we converted the mass of scattered data offered by the geological records into valuable geodynamical information easily accessible for reconstructions creation. In the same time, by programming specific tools we, all at once, facilitated the reconstruction work (tasks automation) and enhanced the model (by highly increasing the kinematic control of plate motions thanks to plate velocity models). Based on the 340 terranes properly defined, we developed a revised set of 35 reconstructions associated to their own velocity models. Using this unique dataset we are now able to tackle major issues of the geology (such as the global sea-level variations and climate changes). We started by studying one of the major unsolved issues of the modern plate tectonics: the driving mechanism of plate motions. We observed that, all along the Earth?s history, plates rotation poles (describing plate motions across the Earth?s surface) tend to follow a slight linear distribution along a band going from the Northern Pacific through Northern South-America, Central Atlantic, Northern Africa, Central Asia up to Japan. Basically, it sighifies that plates tend to escape this median plan. In the absence of a non-identified methodological bias, we interpreted it as the potential secular influence ot the Moon on plate motions. The oceanic realms are the cornerstone of our model and we attached a particular interest to reconstruct them with many details. In this model, the oceanic crust is preserved from one reconstruction to the next. The crustal material is symbolised by the synthetic isochrons from which we know the ages. We also reconstruct the margins (active or passive), ridges and intra-oceanic subductions. Using this detailed oceanic dataset, we developed unique 3-D bathymetric models offering a better precision than all the previously existing ones.