Cuatro aproximaciones a la importancia del movimiento en la evolución y desarrollo del sistema nervioso

El sistema nervioso humano es uno de las mas evolucionados de la escala zoológica, su diferencia fundamental radica en su maravillosa capacidad para procesar información, capacidad que sin duda ha sido determinante para su supervivencia. La interrogante es ¿que factores pueden haber incidido en tan notable evolución? El presente ensayo pretende orientar las posibles respuestas a la interrogante desde cuatro aproximaciones: filogènesis, neuroontegènesis, embriogènesis y cibernética para, finalmente, establecer las responsabilidades y desafíos de la educación en general y de la educación física en particular en la consecución evolutiva de este sorprendente sistema

Evolution du système turbiditique profond du Nil au cours du quaternaire récent

Ce travail, basé sur l’analyse et l’interprétation de prélèvements (carottes kullenberg et calypso) calibrées avec des données acoustiques (sismique 3,5 kHz et multifaisceaux), propose une reconstruction du fonctionnement sédimentaire récent (derniers 250 ka) du système turbiditique profond du Nil (STPN). Pour cela, une étude stratigraphique détaillée et basée sur plusieurs outils a été nécessaire pour dater des séries sédimentaires riches en événements gravitaires et s’étendant sur plusieurs cycles glaciaire/interglaciaire. C’est l’établissement d’une écostratigraphie basée sur les assemblages de foraminifères planctoniques et calibrée avec des outils isotopiques et téphrochronologiques qui a permis d’atteindre une résolution d’étude proche de 2000 ans. Les résultats obtenus montrent que contrairement à la majorité des grands STP argilosilteux modernes, alimentés par une source ponctuelle, le domaine profond de la marge nilotique comprend plusieurs éventails dont certains ont été alimentés en même temps. L’analyse détaillée des faciès et séquences sédimentaires a permis de mettre en évidence un fonctionnement sédimentaire lié aux conditions environnementales affectant le bassin versant du fleuve Nil et son delta. Ainsi, dans le STPN, le forçage climatique nuance le forçage glacio-eustatique classique et à l’origine des modèles stratigraphiques actuels. Les contrastes climatiques de l’Afrique nord orientale permettent notamment l’alimentation d’éventails turbiditiques pendant des périodes de haut niveau marin. Les crues majeures du Nil sont également à l’origine de processus de transport et de dépôt jusque-là peu documentés.Based on the analysis and interpretation of cores (kullenberg and calypso) calibrated with acoustic data (3.5 kHz seismic and swath bathymetry data), this study proposes a reconstruction of the recent sedimentary history (last 250 kyrs) of the Nile deep-sea turbidite system (NDSTS). A detailed stratigraphic study based on several techniques has been necessary to date sedimentary series with abundant gravity events and spreading over several glacial/interglacial cycles. With the establishment of an ecostratigraphy based on planktonic foraminifer assemblages and calibrated with isotopic and tephrochronologic tools we have reached a study resolution close to 2000 yrs. The results obtained permit the interpretation of all channel-levee systems located on the margin as a multi-source system. Indeed, in contrast to the majority of large modern muddy DSTS, fed by a punctual source, the Nile margin has several small-sized channel-levee systems and some of them were fed at the same time. The detailed analysis of sedimentary facies and sequences provide evidence for a sedimentary functioning linked to environmental conditions affecting the drainage basin of the Nile River and its delta. Thus, in the NDSTS, the climate forcing qualifies the classical glacio-eustatic forcing at the source of modern stratigraphic models. Climatic contrasts in NE Africa allow in particular the feeding of turbiditic channel-levee systems during high sea-level stands. Major Nile floods are also the source of transport and depositional processes poorly documented until now

Etude biochimique d'un cytochrome P450 de cerveau humain (le CYP2U1)

Parmi les 57 cytochromes P450 identifiés lors du séquençage complet du génome humain, on en dénombre environ 15 dont on ne connaît pratiquement rien de leurs rôles physiologiques, de leurs substrats, et de leurs structures, d où le nom de P450 orphelins . Le CYP2U1 est l un des cytochromes P450 les plus fortement exprimé au niveau du cerveau et du cervelet mais c est aussi l un des plus conservé parmi les différentes espèces du règne animal. Ce travail de thèse a tout d abord consisté à optimiser les conditions d expression du CYP2U1 sous une forme active. Un premier système d expression dans la levure Saccharomyces Cerevisiae a permis une production d un complexe CYP2U1-P450 réductase catalytiquement actif permettant des études de recherche de substrat. Un second système d expression dans Escherichia Coli devrait permettre d obtenir de plus grandes quantités d enzyme soluble destinée à des études structurales. Dans un second temps, une recherche de substrats a été effectuée à l aide d analyse d incubats par chromatographie liquide couplée à une détection par spectrométrie de masse. A ce jour, un screening dirigé de plus de soixante-dix molécules, substrats de P450s de la famille 2, a permis d identifier les premiers substrats exogènes du CYP2U1, les analogues de terfénadone et la débrisoquine. D autre part, une étude par modélisation moléculaire de la structure du CYP2U1 a été effectuée. Cette étude montre que le CYP2U1 diffère de tous les autres P450s par la présence d un insert très spécifique dans son domaine N-terminal. Des modèles par homologie basés sur les structures cristallographiques des P450s de la famille 2 ont été construits. Ces modèles ont été validés par dynamique moléculaire et ont permis de proposer un mode d interaction avec la membrane, d identifier la position des canaux d accès ainsi que de déterminer la topologie du site actif. Enfin, un docking des premiers substrats exogènes au sein du site actif du CYP2U1 a permis de confirmer la régioselectivité des hydroxylations catalysées par le CYP2U1.Among the 57 human cytochrome P450 genes that have been identified; substrates, structure and physiologic role of 15 of them is practically unknown. They are called orphan. One of them, CYP2U1 is one of the most expressed cytochrome P450 in the brain and in the cerebellum but also one of the most conserved isoform in the all animal kingdom. This manuscript first describes the optimization of the heterologous expression of an active form of CYP2U1. Expression in a eukaryotic host, yeast Saccharomyces Cerevisiae first allows the production of a catalytic active CYP2U1-P450 reductase complex needed for substrate screening. Another expression system in a prokaryote host Escherichia Coli will allow higher production rate of a truncated and soluble form of the protein which will permit structural studies. Then a directed substrate screening was performed with the liquid chromatography mass spectrometry analysis of CYP2U1 incubations. To date, 70 molecules, CYP2 family substrates, were tested that allow the identification of the two first exogenous CYP2U1 substrates: débrisoquine and terfenadone analogs. A structural study was achieved using a homology tridimensional model of the enzyme. We have found that CYP2U1 is longer than the other human CYPs, with an N-terminal 20 amino acids insertion, located after the helical membrane spanning domain. Structural models were built using six crystallized human CYP2s as templates. Molecular dynamics experiments in membrane suggested a specific interaction with the membrane. The active site topology and the access channels were also determined and a docking of the two first exogenous CYP2U1 substrates was performed in order to confirm the regioselective hydroxylation activities observed in vitro.PARIS5-Bibliotheque electronique (751069902) / SudocPARIS-BIUM-Bib. électronique (751069903) / SudocSudocFranceF

Final Safety and Health-Related Quality of LIfe Results of the Phase 2/3 Act.In.Sarc Study With Preoperative NBTXR3 Plus Radiation Therapy Versus Radiation Therapy in Locally Advanced Soft-Tissue Sarcoma

Calidad de vida; Sarcoma de tejido blando localmente avanzado; RadioterapiaQualitat de vida; Sarcoma de teixit tou localment avançat; RadioteràpiaQuality of life; Locally advanced soft-tissue sarcoma; Radiation therapyPurpose Act.In.Sarc (NCT02379845) demonstrated that the first-in-class radioenhancer NBTXR3, activated by preoperative radiation therapy (RT), doubled the rate of pathologic complete response after resection compared with preoperative RT alone in adult patients with locally advanced soft tissue sarcoma of the extremity or trunk wall (16.1% vs 7.9%, P = .045), and more patients achieved R0 resections (77.0% vs 64.0%, P = .042). These are the toxicity and health-related quality of life (HRQoL) results. Methods and Materials Act.In.Sarc randomized eligible patients 1:1 to either NBTXR3 (single intratumoral injection, volume equivalent to 10% of baseline tumor volume, at 53.3 g/L) activated by external-beam RT (arm A) or external-beam RT alone (arm B) (50 Gy in 25 fractions), followed by surgery in both arms. Here, we report the safety analyses in the all-treated population with a long-term follow-up of at least 2 years, and HRQoL in the intention-to-treat full analysis set. Results During the on-treatment period, serious adverse events (SAEs) of all grades related to NBTXR3 occurred in 10.1% (9/89) of patients (arm A), and SAEs related to RT occurred in 5.6% (5/89) (arm A) versus 5.6% (5/90) (arm B); postsurgery hospitalization owing to SAEs occurred in 15.7% (14/89) (arm A) versus 24.4% (22/90) (arm B). During the follow-up period, posttreatment SAEs (regardless of relationship) occurred in 13.5% (12/89) (arm A) versus 24.4% (22/90) (arm B). NBTXR3 did not negatively affect HRQoL; during the follow-up period, there was an improvement in most mean Toronto extremity salvage, EuroQoL 5-dimension (EQ-5D), EQ5D02-EQ visual analog scale, reintegration to normal living index, and musculoskeletal tumor rating scale scores. Conclusions NBTXR3 did not negatively affect safety or HRQoL. Long-term safety results reinforce the favorable benefit–risk ratio of NBTXR3 plus RT

Variability in intermediate water circulation of the western Tyrrhenian margin (NE Corsica) over the past 56 kyr

The Marion Dufrene core MD01-2472 made of hemipelagic fine-grained sediments (silt and clays) was collected at 501 m depth on the East Corsica continental slope in 2001 and studied in detail in its 12 uppermost meters. The correlation between sedimentological parameters (Sortable Silt), isotopic data and 14C dating allowed to establish the chronology of main climate events (Younger Dryas/YD, Bölling-Alleröd/B-A, Heinrich events/HS) on this record and to evaluate the impact of major climate oscillations on bottom water condition variability. The sea temperature changes are identified thanks to the planktonic foraminifera assemblages. HS are marked by planktonic foraminifers with peaks of the polar species N. pachyderma (left-coiling), whilst interstadials are marked by warm planktonics that become very abundant during the B-A and Holocene. The occurrence of reworked ostracod species (originating from the continental shelf) and the presence of shallow water Elphidium/Ammonia benthic foraminifera are used to estimate the degree of along-slope transport at the core site. This has revealed two intervals of along-slope transport also associated with coarse-grained contourites, deposited during the YD and HS2 episodes. Intervals with Krithe spp. (ostracod), C. wuellerstorfi (benthic foraminifera) indicate bottom water oxygenation during stadials, whereas interstadials are typified by A. acuminata and Paracypris sp (ostracods) indicating low oxygenated environments. The Last Glacial Maximum is dominated by the planktonic foraminifer T. quinqueloba suggesting high surface primary productivity associated with the establishment of mestrophic bottom conditions. During the Holocene, benthic assemblages indicate oligo-mesotrophic conditions and weak hydrodynamic bottom regime. We hypothesize that there is relationship between the Levantine Intermediate Water (LIW) intensification during cold rapid climate events and benthic fauna assemblages due to changes in: 1) bottom water ventilation, corresponding to a significant reinforcement of the LIW velocity, and 2) the export of nutrients (generating changes in trophic conditions) and/or sediment particles by bottom currents (contributing to the formation of contourites)

Structural and functional analysis of SGT1–HSP90 core complex required for innate immunity in plants

SGT1 (Suppressor of G2 allele of skp1), a co-chaperone of HSP90 (Heat-shock protein 90), is required for innate immunity in plants and animals. Unveiling the cross talks between SGT1 and other co-chaperones such as p23, AHA1 (Activator of HSP90 ATPase 1) or RAR1 (Required for Mla12 resistance) is an important step towards understanding the HSP90 machinery. Nuclear magnetic resonance spectroscopy and mutational analyses of HSP90 revealed the nature of its binding with the CS domain of SGT1. Although CS is structurally similar to p23, these domains were found to non-competitively bind to various regions of HSP90; yet, unexpectedly, full-length SGT1 could displace p23 from HSP90. RAR1 partly shares the same binding site with HSP90 as the CS domain, whereas AHA1 does not. This analysis allowed us to build a structural model of the HSP90–SGT1 complex and to obtain a compensatory mutant pair between both partners that is able to restore virus resistance in vivo through Rx (Resistance to potato virus X) immune sensor stabilization

Extracellular riboflavin induces anaerobic biofilm formation in Shewanella oneidensis

Background Some microorganisms can respire with extracellular electron acceptors using an extended electron transport chain to the cell surface. This process can be applied in bioelectrochemical systems in which the organisms produce an electrical current by respiring with an anode as electron acceptor. These organisms apply flavin molecules as cofactors to facilitate one-electron transfer catalyzed by the terminal reductases and in some cases as endogenous electron shuttles. Results In the model organism Shewanella oneidensis, riboflavin production and excretion trigger a specific biofilm formation response that is initiated at a specific threshold concentration, similar to canonical quorum-sensing molecules. Riboflavin-mediated messaging is based on the overexpression of the gene encoding the putrescine decarboxylase speC which leads to posttranscriptional overproduction of proteins involved in biofilm formation. Using a model of growth-dependent riboflavin production under batch and biofilm growth conditions, the number of cells necessary to produce the threshold concentration per time was deduced. Furthermore, our results indicate that specific retention of riboflavin in the biofilm matrix leads to localized concentrations, which by far exceed the necessary threshold value. Conclusion This study describes a new quorum-sensing mechanism in S. oneidensis. Biofilm formation of S. oneidensis is induced by low concentrations of riboflavin resulting in an upregulation of the ornithine-decarboxylase speC. The results can be applied for the development of strains catalyzing increased current densities in bioelectrochemical systems

Histoire Géologique du massif Armoricain : Actualité de la recherche

National audienceUne part essentielle de l'histoire géologique de la France (et même d'Europe occidentale, avec des roches ayant environ 2000 Ma) est déchiffrable dans le Massif armoricain. Si celui-ci est réputé pour ses excellentes qualités d'affleurement sur le littoral (Armor, ou pays de la mer), certains objets ou structures ne peuvent être observés que dans le bocage (Argoat, ou pays des arbres), où leur lisibilité est souvent problématique. En Armor comme en Argoat, de nombreux sites constituent un réel patrimoine géologique (l'intérêt de certaines localités sera mis en exergue dans le texte), dont la valeur ne peut être jaugée qu'au regard de son intérêt scientifique. Ainsi ce travail - une mise en perspective de nos connaissances scientifiques sur l'évolution géologique du Massif armoricain - est-il basé sur plusieurs synthèses antérieures (par ex. Le Corre et al., 1991 ; Ballèvre et al., 2009), qu'il complète en intégrant les nouvelles données disponibles. Plus qu'un exposé complet des faits, nous visons à clarifier certains débats, et montrer en quoi les recherches en cours changent notre image globale du Massif armoricain. Nous restreindrons notre analyse à la période qui couvre la fin du Protérozoïque (Ediacarien : 635-540 Ma), le Paléozoïque (540-250 Ma) et le début du Mésozoïque (Trias : 250-200 Ma)