Corticotectal Projections From the Premotor or Primary Motor Cortex After Cortical Lesion or Parkinsonian Symptoms in Adult Macaque Monkeys: A Pilot Tracing Study

The corticotectal projections, together with the corticobulbar (corticoreticular) projections, work in parallel with the corticospinal tract (CST) to influence motoneurons in the spinal cord both directly and indirectly via the brainstem descending pathways. The tectospinal tract (TST) originates in the deep layers of the superior colliculus. In the present study, we analyzed the corticotectal projections from two motor cortical areas, namely the premotor cortex (PM) and the primary motor cortex (M1) in eight macaque monkeys subjected to either a cortical lesion of the hand area in M1 (n = 4) or Parkinson’s disease-like symptoms PD (n = 4). A subgroup of monkeys with cortical lesion was subjected to anti-Nogo-A antibody treatment whereas all PD monkeys were transplanted with Autologous Neural Cell Ecosystems (ANCEs). The anterograde tracer BDA was used to label the axonal boutons both en passant and terminaux in the ipsilateral superior colliculus. Individual axonal boutons were charted in the different layers of the superior colliculus. In intact animals, we previously observed that corticotectal projections were denser when originating from PM than from M1. In the present M1 lesioned monkeys, as compared to intact ones the corticotectal projection originating from PM was decreased when treated with anti-Nogo-A antibody but not in untreated monkeys. In PD-like symptoms’ monkeys, on the other hand, there was no consistent change affecting the corticotectal projection as compared to intact monkeys. The present pilot study overall suggests that the corticotectal projection is less affected by M1 lesion or PD symptoms than the corticoreticular projection previously reported in the same animals

Systèmes temps réel embarqués : spécification, conception, implémentation et validation temporelle

Cet ouvrage présente une méthodologie complète et opérationnelle de développement des systèmes temps réel de contrôle-commande. Il permet au lecteur de : - connaître et mettre en oeuvre les méthodes de spécification et de conception ; - définir et paramétrer l'environnement d'exécution des systèmes ; - réaliser l'implémentation multitâche basée sur un noyau temps réel ; - développer l'application en C, Ada ou LabVIEW . L'ouvrage fait également le point sur les dernières avancées dans le domaine des systèmes temps réel multitâches. De nombreux exemples industriels sont traités, permettant de comprendre puis de mettre en oeuvre les principes de cette méthodologie de développement. Ce livre s'adresse à tous les ingénieurs ou techniciens concepteurs d'applications temps réel de contrôle-commande de procédés industriels. Il est également destiné aux étudiants en informatique industrielle

Genetic polymorphisms of MMP1, MMP3 and MMP7 gene promoter and risk of colorectal adenoma

BACKGROUND: Matrix metalloproteinases (MMP) have been shown to play a role in colorectal cancer (CRC). More recently, MMP1, MMP3 and MMP7 functional gene promoter polymorphisms have been found to be associated with CRC occurrence and prognosis. To document the role of MMP polymorphisms in the early step of colorectal carcinogenesis, we investigated their association with colorectal adenoma risk in a case-control study comprising 295 patients with large adenomas (LA), 302 patients with small adenomas (SA) and 568 polyp-free (PF) controls. METHODS: Patients were genotyped using automated fragment analysis for MMP1 -1607 ins/del G and MMP3 -1612 ins/delA (MMP3.1) polymorphisms and allelic discrimination assay for MMP3 -709 A/G (MMP3.2) and MMP7 -181 A/G polymorphisms. Association between MMP genotypes and colorectal adenomas was first tested for each polymorphism separately and then for combined genotypes using the combination test. Adjustment on relevant variables and estimation of odds ratios were performed using unconditional logistic regression. RESULTS: No association was observed between the polymorphisms and LA when compared to PF or SA. When comparing SA to PF controls, analysis revealed a significant association between MMP3 -1612 ins/delA polymorphism and SA with an increased risk associated with the 6A/6A genotype (OR = 1.67, 95%CI: 1.20–2.34). Using the combination test, the best association was found for MMP3.1-MMP1 (p = 0.001) with an OR of 1.88 (95%CI: 1.08–3.28) for the combined genotype 2G/2G-6A/6A estimated by logistic regression. CONCLUSION: These data show a relation between MMP1 -1607 ins/del G and MMP3 -1612 ins/delA combined polymorphisms and risk of SA, suggesting their potential role in the early steps of colorectal carcinogenesis

Size-Based Characterization of an Ionic Polydiacetylene by Taylor Dispersion Analysis and Capillary Electrophoresis

International audienceThis work focuses on the size-based characterization of a water-soluble ionic polydiacetylene with a polycationic structure, poly-[(1,6-bis(N-methylimidazolium)hexa-2,4-diyne)dibromide]. This polymer could not be characterized using classical analytical techniques such as size-exclusion chromatography and MALDI−TOF mass spectrometry due to problems of purification, low quantities available, and difficult laser desorption. The work presented here demonstrates the interest and the complementarity of two independent analytical methods, Taylor dispersion analysis (TDA) and capillary electrophoresis (CE), that require only very small amounts of sample (only a few nanoliters are injected) and that can be easily implemented on commercially available capillary electrophoresis apparatus. TDA is a nonseparative method that allows the absolute determination of the average hydrodynamic radius of the polymer. This method does not require the determination of the polymer concentration in the sample and is not perturbed by the presence of residual monomer. Since the average hydrodynamic radius determined by this method is a weight average value, it also gives information complementary to the average value derived from dynamic light scattering measurements. Simple hydrodynamic modeling allows estimation of a minimal value for the average degree of polymerization. Free solution CE can be used for monitoring the polymerization process and quantifying the degree of conversion. Furthermore, entangled polymer solution CE was used as a size-based separation technique for the characterization of the molar mass distribution using calibration with polyvinylpyridine standards. Number and weight molar mass distributions of the sample were obtained relative to this calibration

Separation of three strains of polio virus by capillary zone electrophoresis and study of their interaction with aluminum oxyhydroxide

International audienceThe development of combination vaccines is essential to reduce the number of injections, shorten vaccination schedules and increase vaccination coverage. Vaccine adjuvants are used to modulate and enhance the immune response induced by the antigens. To support the development of combination vaccines, the study of antigen-adjuvant interactions in the final vaccine formulations is required as interaction competitions may take place between the different antigens. In the present work, a capillary zone electrophoresis (CZE) methodology was firstly optimized on six model proteins, namely bovine serum albumin, β-lactoglobulin, myoglobin, ribonuclease A, cytochrome C and lysozyme. A cationic dynamic coating (polybrene) and a zwitterionic amino acid additive (β-alanine) in the background electrolyte were used to reduce the phenomena of protein adsorption on the inner wall of the capillary and thus optimize the separation efficiency of the proteins. The developed methodology was then used to separate three strains from inactivated polio virus, each strain being a whole virus composed of copies of 4 viral proteins and study their interaction with aluminum oxyhydroxide. The antigen-adjuvant interactions could be modulated by addition of phosphate ions playing the role of competitors for the poliovirus

Study of interactions between antigens and polymeric adjuvants in vaccines by frontal analysis continuous capillary electrophoresis

International audienceVaccine adjuvants are used to enhance the immune response induced by antigens that have insufficient immunostimulatory capabilities. The present work aims at developing a frontal analysis continuous capillary electrophoresis (FACCE) methodology for the study of antigen–adjuvant interactions in vaccine products. After method optimization using three cationic model proteins, namely lysozyme, cytochrome c, and ribonuclease A, FACCE was successfully implemented to quantify the free antigen and thus to determine the interaction parameters (stoichiometry and binding constant) between an anionic polymeric adjuvant (polyacrylic acid, SPA09) and a cationic vaccine antigen in development for the treatment for Staphylococcus aureus. The influence of the ionic strength of the medium on the interactions was investigated. A strong dependence of the binding parameters with the ionic strength was observed. The concentration of the polymeric adjuvant was also found to significantly modify the ionic strength of the formulation, the extent of which could be estimated and corrected

Systèmes temps réel embarqués : Conception et implémentation

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Biotransformation of guttiferones, Symphonia globulifera metabolites, by Bipolaris cactivora , an endophytic fungus isolated from its leaves

International audienceThe search for active microorganisms for the biotransformation of guttiferone A (1) and C (6) has been successfully undertaken from a collection of endophytic fungi of Symphonia globulifera. Of the twenty-five isolates obtained from the leaves, three are active and have been identified as Bipolaris cactivora. The products obtained are the result of xanthone cyclisation with the formation of two regioisomers among four possible and corresponding to 1,16-oxy-guttiferone and 3,16-oxy-guttiferone. The biotransformation conditions were studied. Interestingly, both oxy-guttiferones A are present in the plant, and the ratio of 3,16-oxy-guttiferone to 1,16-oxy-guttiferone is 4 : 1, very close to that observed by biotransformation (3.8 : 1). These results are consistent with the involvement of endophytes in their formation pathway from guttiferone A, in planta. Finally, biotransformation made it possible to obtain and describe for the first time oxy-guttiferones C

Size and Charge Characterization of Lipid Nanoparticles for mRNA Vaccines

International audienceMessenger RNA vaccines have come into the spotlight as a promising and adaptive alternative to conventional vaccine approaches. The efficacy of mRNA vaccines relies on the ability of mRNA to reach the cytoplasm of cells, where it can be translated into proteins of interest allowing to trigger the immune response. However, unprotected mRNA is unstable, susceptible to degradation by exo and endonucleases, and its negative charges are electrostatically repulsed by the anionic cell membranes. Therefore, mRNA needs a delivery system that protects the nucleic acid from degradation and allows it to enter into the cells. Lipid nanoparticles (LNPs) represent the non-viral leading vector for mRNA delivery. Physicochemical parameters of LNPs, including their size and their charge, directly impact their in vivo behavior and, therefore, their cellular internalization. In this work, Taylor Dispersion Analysis (TDA) was used as a new methodology for the characterization of the size and polydispersity of LNPs, and capillary electrophoresis (CE) was used for the determination of LNPs global charge. The results obtained were compared with those obtained by dynamic light scattering (DLS) and Laser Doppler Electrophoresis (LDE)

Antigen-Adjuvant Interactions in Vaccines by Taylor Dispersion Analysis: Size Characterization and Binding Parameters

International audienceVaccine adjuvants are immunostimulatory substances used to improve and modulate the immune response induced by antigens. A better understanding of the antigen-adjuvant interactions is necessary to develop future effective vaccine. In this study, Taylor dispersion analysis (TDA) was successfully implemented to characterize the interactions between a polymeric adjuvant (poly(acrylic acid), SPA09) and a vaccine antigen in development for the treatment of Staphylococcus aureus. TDA allowed one to rapidly determine both (i) the size of the antigen-adjuvant complexes under physiological conditions and (ii) the percentage of free antigen in the adjuvant/antigen mixture at equilibrium and finally get the interaction parameters (stoichiometry and binding constant). The complex sizes obtained by TDA were compared to the results obtained by transmission electron microscopy, and the binding parameters were compared to results previously obtained by frontal analysis continuous capillary electrophoresis