The design, fabrication, and characterization of polymer-carbon nanotube (CNT) composites have generated a significant amount of attention in the fields of materials science and polymer chemistry. The challenge in fabricating composites that exploit the unique properties of the CNT and the ideal processing ability and low cost of the polymer is in achieving a uniform dispersion of the filler in the polymer matrix. This body of work focuses on (1) techniques employed to disperse CNTs into a polymer matrix and (2) the effects of CNTs on the mechanical and electrical properties of the polymer. Poly (methyl methacrylate) (PMMA), an amorphous polymer, and poly (4-methyl-1-pentene) (P4M1P), a semi crystalline polymer, were chosen as the matrices. Non-functionalized single-walled carbon nanotubes and soot (unpurified carbon nanotubes) were chosen as the filler material. In the first study, single-walled carbon nanotubes (SWNTs) were sonicated in methyl methacrylate monomer and initiated via thermal energy, UV light, and gamma radiation. Composite films with increased dielectric constants and unique optical transparency were produced. Samples were characterized using differential scanning calorimetry, dielectric analysis, and dynamic mechanical analysis. Refractive Indices were obtained and correlated to the dielectric constant using Maxwells relationship. PMMA/soot composites were fabricated in the second study. Dispersion was accomplished by way of sonication and melt compounding. The PMMA/soot composites were exposed to gamma radiation, with a 137Cs gamma source, in order to investigate how the filler affects the polymers ability to resist radiation. Samples were characterized by differential scanning calorimetry, dielectric analysis, and dynamic mechanical.

Over the years, secondary metabolites have proven to be significant in the discovery of novel antibiotics and/or lead compounds. Various secondary metabolites have been reported to be produced by fungus of the genus, Alternaria. Here we report the isolation of secondary metabolites by the bioassay-guided fractionation of the ethyl acetate extract of fermentation cultures of the fungus, Alternaria tenuissima. This fungal strain was isolated from the soil underlying the lichen, Peltigera didactyla; and the lichen was collected from Wapusk National Park, a location in Northern Manitoba. The compounds isolated from the fungus include deoxyphomalone, dimethyl 4-methyl-2,6-pyridinedicarboxylate, stemphyperylenol and N-Methyl pyrrolidinone. Their structures were determined by comprehensive analysis of their spectroscopic data including FT-IR, mass spectrometry, 1D and 2D NMR; and their bioactivities were tested against E. coli cells. Some of the compounds demonstrated some bioactivity. The taxonomic identity of the fungus was confirmed by ITS sequencing of its ribosomal DNA.

Over the years, secondary metabolites have proven to be significant in the discovery of novel antibiotics and/or lead compounds. Various secondary metabolites have been reported to be produced by fungus of the genus, Alternaria. Here we report the isolation of secondary metabolites by the bioassay-guided fractionation of the ethyl acetate extract of fermentation cultures of the fungus, Alternaria tenuissima. This fungal strain was isolated from the soil underlying the lichen, Peltigera didactyla; and the lichen was collected from Wapusk National Park, a location in Northern Manitoba. The compounds isolated from the fungus include deoxyphomalone, dimethyl 4-methyl-2,6-pyridinedicarboxylate, stemphyperylenol and N-Methyl pyrrolidinone. Their structures were determined by comprehensive analysis of their spectroscopic data including FT-IR, mass spectrometry, 1D and 2D NMR; and their bioactivities were tested against E. coli cells. Some of the compounds demonstrated some bioactivity. The taxonomic identity of the fungus was confirmed by ITS sequencing of its ribosomal DNA.

O gênero Erythroxylum P. Browne pertence a família Erythroxylaceae Kunth e é principalmente conhecido devido as espécies E. coca e E. novogranatense, as “plantas da coca”. O gênero é a única fonte natural da cocaína e de outros alcaloides com núcleo ecgonina, principais responsáveis pelos efeitos tóxicos e biológicos originados pelo consumo de suas espécies. A presença da cocaína é amplamente aceita para as plantas de coca, porém a sua biossíntese por outras espécies apresenta divergência, o que pode estar relacionada ao período de coleta. Além destas particularidades fitoquímicas, as espécies do gênero também apresentam importantes atividades como antioxidante e antimicrobiana, além de toxicidade a humanos e a ovinos. O Brasil é o centro da diversidade e do endemismo do gênero e no sul do país, nos estados do Rio Grande do Sul e de Santa Catarina, as carcaterísticas fitoquímicas e potencialidades tóxicas e farmacológicas das espécies apresentam um campo aberto para estudos. Desta forma, foram avaliadas características fitoquímicas e potencialidades tóxicas e farmacológicas de espécies nativas dos estados do Rio Grande do Sul e de Santa Catarina, coletadas em dois períodos climáticos distintos, verão e inverno, além de revisão bibliográfica sobre as espécies produtoras de cocaína e as implicações segundo a legislação brasileira vigente. Foram utilizadas metodologia de planária, disco-difusão em ágar, microdiluição em caldo, medida da extinção da absorção do cátion 2,2-difenil-1-picrilhidrazil e procedimentos preconizados pelas Nações Unidas para a investigação fitoquímica de espécies produtoras de cocaína. Foi verificado que 24 espécies apresentam o aparato enzimático para a produção da cocaína. Embora E. novogranatense origina rendimentos apropriados ao tráfico, segundo a legislação Brasileira vigente, apenas E. coca encontra-se proscrita, o que torna necessário a inclusão de E. novogranatense na lista de plantas proscritas. Para o estudo toxicológico desenvolvido com E. deciduum sobre modelo de planária, foi necessário adaptar a metodologia existente. O extrato da espécie ocasionou aumento significativo da velocidade de locomoção (p= 0.016) e comportamentos estereotipados padronizados de posição tipo C e hipercinesia tipo parafuso, eventos característicos da neurotransmissão dopaminérgica em planárias. Os resultados, além de ampliar as possibilidades do uso destes vermes na busca por extratos ativos, demonstram que E. deciduum biossintetiza metabólitos ativos sobre este neurotransmissor, os quais podem estar relacionados com os efeitos ocasionados pelo consumo da espécie vegetal. A influência do período de coleta sobre as potencialidades farmacológicas e as características fitoquímicas foi investigada e os resultados demonstram esta infuência. Diferentes extratos de E. argentinum e E. deciduum, coletadas durante o verão, apresentaram atividade antimicrobiana superiores a verificada para os extratos obtidos de coletas realizadas no inverno. O extrato etanólico de E. argentinum, coleta verão, pode ser considerado um verdadeiro antimicrobiano, MIC= 0,78mg/ mL, e desta forma torna-se uma fonte promissora para a descoberta de novas moléculas antimicrobianas. Os extratos das espécies E. argentinum e E. deciduum demonstram pertinentes resultados sobre a atividade antioxidante. A influência do período de coleta, verão/ inverno, sobre a atividade foi identificada. A influência do período de coleta sobre as atividades tóxico-farmacológicas é corroborada pelo perfil alcaloídico obtido de noves espécies do gênero, coletadas durante o verão e o inverno, nos estados do Rio Grande do Sul e de Santa Catarina. O perfil alcaloídico das espécies E. amplifolium, E. argentinum, E. cuneifolium, E. cuspidifolium, E. deciduum, E. microphyllum, E. myrsinites, E. pelleterianum e E. vacciniifolium demonstra a presença dos alcaloides: éster de metecgonidina, éster de metilecgonina, cuscohigrina e tropacocaína e dos intermediários da biossíntese: higrina, tropinona e tropanol. A identificação dos metabólitos éster de metilecgonina e éster de metilecgonidina também demonstra que as espécies do gênero Erythroxylum presentes no Sul do Brasil apresentam potencialidade econômicas, pois podem ser empregadas na produção de padrões toxicológicos. Os objetivos propostos foram cumpridos e permitem concluir que espécies do gênero Erythroxylum dos estados do Rio Grande do Sul e de Santa Catarina, Sul do Brasil, demonstram importância tóxica, farmacológica e química, sendo parte destas influenciada pelo período de coleta, verão/ inverno. / “Chemical and Biological Study of Erythroxylum P. Browne Species Collected in Southern Brazil”. Erythroxylum P. Browne genus belongs to the Erythroxylaceae Kunth family and is mainly known due to E. coca and E. novogranatense species, the "coca plants". The genus is the only natural source of cocaine and other alkaloids with ecgonine nucleus, mainly responsible for the toxic and biological effects caused by the consumption of their species. The presence of cocaine is widely accepted for coca plants, but its biosynthesis by other species shows divergence, which may be related to the collect period. Besides these phytochemical peculiarities, the species of the genus also present important activities such as antioxidant and antimicrobial, besides toxicity to humans and sheep. Brazil is the center of diversity and endemism of the genus and in the south of the country, in the states of Rio Grande do Sul and Santa Catarina, the phytochemical characteristics, toxic and pharmacological potentials of the species present an open field for studies. Thus, phytochemical characteristics, toxic and pharmacological potentials of native species of the states of Rio Grande do Sul and Santa Catarina were assessed, collected in two distinct climatic periods, summer and winter, as well as a bibliographical review on cocaine producing species and implications under current Brazilian law. Some methodologies were used such as planaria, disc-diffusion in agar, microdilution in broth, extinction measurement of the absorption of cation 2,2-diphenyl-1-picrylhydrazyl and procedures recommended by the United Nations for the phytochemical investigation of cocaine producing species. It was verified that twenty-four species present the enzymatic apparatus for the production of cocaine. Although E. novogranatense originate income appropriate to traffic according to current Brazilian legislation, only E. coca is outlawed, which makes it necessary to include E. novogranatense in the list of proscribed plants. For the toxicological study developed with E. deciduum on planaria model, it was necessary to adapt the existing methodology. The extract of the species caused a significant increase in locomotion velocity (p= 0.016) and standardized stereotyped behaviors of type C position and screw- type hyperkinesia, characteristic events of dopaminergic neurotransmission in planarians. The results, besides expanding the possibilities of the use of these worms in search for active extracts, demonstrate that E. deciduum biosynthesizes active metabolites on this neurotransmitter, which may be related to the effects caused by the consumption of the plant species. The influence of the collect period on pharmacological potentials and phytochemical characteristics was investigated and the results demonstrate this influence. Different extracts of E. argentinum and E. deciduum collected during summer showed higher antimicrobial activity than the extracts obtained from winter collect. The ethanolic extract of E. argentinum, summer collect, may be considered a true antimicrobial, MIC= 0.78mg/ mL, on Staphylococcus aureus, and in this way it becomes a promising source for the discovery of new antimicrobial molecules. The extracts of E. argentinum and E. deciduum species demonstrate relevant results on antioxidant activity. The influence of the collecting period, summer/ winter, on the activity was verified. The influence of collect period on toxic- pharmacological activities is corroborated by the alkaloid profile obtained from nine species of the genus, collected during summer and winter in the states of Rio Grande do Sul and Santa Catarina. The alkaloid profile of E. amplifolium, E. argentinum, E. cuneifolium, E. cuspidifolium, E. deciduum, E. microphyllum, E. myrsinites, E. pelleterianum and E. vacciniifolium species shows the presence of alkaloids: ecgonidine methyl ester, ecgonine methyl ester, cuscohygrine and tropacocaine and the biosynthesis intermediates: hygrine, tropinone and tropanol. The identification of the ecgonine methyl ester and ecgonidine methyl ester also shows that Erythroxylum genus species present in southern Brazil have economic potential because they can be used in the production of toxicological standards. The aims were met and allow the conclusion that Erythroxylum genus of Rio Grande do Sul and Santa Catarina states, south of Brazil, show toxic, pharmacological and chemical importance, part of these being influenced by the collect period, summer/ winter.

O gênero Erythroxylum P. Browne pertence a família Erythroxylaceae Kunth e é principalmente conhecido devido as espécies E. coca e E. novogranatense, as “plantas da coca”. O gênero é a única fonte natural da cocaína e de outros alcaloides com núcleo ecgonina, principais responsáveis pelos efeitos tóxicos e biológicos originados pelo consumo de suas espécies. A presença da cocaína é amplamente aceita para as plantas de coca, porém a sua biossíntese por outras espécies apresenta divergência, o que pode estar relacionada ao período de coleta. Além destas particularidades fitoquímicas, as espécies do gênero também apresentam importantes atividades como antioxidante e antimicrobiana, além de toxicidade a humanos e a ovinos. O Brasil é o centro da diversidade e do endemismo do gênero e no sul do país, nos estados do Rio Grande do Sul e de Santa Catarina, as carcaterísticas fitoquímicas e potencialidades tóxicas e farmacológicas das espécies apresentam um campo aberto para estudos. Desta forma, foram avaliadas características fitoquímicas e potencialidades tóxicas e farmacológicas de espécies nativas dos estados do Rio Grande do Sul e de Santa Catarina, coletadas em dois períodos climáticos distintos, verão e inverno, além de revisão bibliográfica sobre as espécies produtoras de cocaína e as implicações segundo a legislação brasileira vigente. Foram utilizadas metodologia de planária, disco-difusão em ágar, microdiluição em caldo, medida da extinção da absorção do cátion 2,2-difenil-1-picrilhidrazil e procedimentos preconizados pelas Nações Unidas para a investigação fitoquímica de espécies produtoras de cocaína. Foi verificado que 24 espécies apresentam o aparato enzimático para a produção da cocaína. Embora E. novogranatense origina rendimentos apropriados ao tráfico, segundo a legislação Brasileira vigente, apenas E. coca encontra-se proscrita, o que torna necessário a inclusão de E. novogranatense na lista de plantas proscritas. Para o estudo toxicológico desenvolvido com E. deciduum sobre modelo de planária, foi necessário adaptar a metodologia existente. O extrato da espécie ocasionou aumento significativo da velocidade de locomoção (p= 0.016) e comportamentos estereotipados padronizados de posição tipo C e hipercinesia tipo parafuso, eventos característicos da neurotransmissão dopaminérgica em planárias. Os resultados, além de ampliar as possibilidades do uso destes vermes na busca por extratos ativos, demonstram que E. deciduum biossintetiza metabólitos ativos sobre este neurotransmissor, os quais podem estar relacionados com os efeitos ocasionados pelo consumo da espécie vegetal. A influência do período de coleta sobre as potencialidades farmacológicas e as características fitoquímicas foi investigada e os resultados demonstram esta infuência. Diferentes extratos de E. argentinum e E. deciduum, coletadas durante o verão, apresentaram atividade antimicrobiana superiores a verificada para os extratos obtidos de coletas realizadas no inverno. O extrato etanólico de E. argentinum, coleta verão, pode ser considerado um verdadeiro antimicrobiano, MIC= 0,78mg/ mL, e desta forma torna-se uma fonte promissora para a descoberta de novas moléculas antimicrobianas. Os extratos das espécies E. argentinum e E. deciduum demonstram pertinentes resultados sobre a atividade antioxidante. A influência do período de coleta, verão/ inverno, sobre a atividade foi identificada. A influência do período de coleta sobre as atividades tóxico-farmacológicas é corroborada pelo perfil alcaloídico obtido de noves espécies do gênero, coletadas durante o verão e o inverno, nos estados do Rio Grande do Sul e de Santa Catarina. O perfil alcaloídico das espécies E. amplifolium, E. argentinum, E. cuneifolium, E. cuspidifolium, E. deciduum, E. microphyllum, E. myrsinites, E. pelleterianum e E. vacciniifolium demonstra a presença dos alcaloides: éster de metecgonidina, éster de metilecgonina, cuscohigrina e tropacocaína e dos intermediários da biossíntese: higrina, tropinona e tropanol. A identificação dos metabólitos éster de metilecgonina e éster de metilecgonidina também demonstra que as espécies do gênero Erythroxylum presentes no Sul do Brasil apresentam potencialidade econômicas, pois podem ser empregadas na produção de padrões toxicológicos. Os objetivos propostos foram cumpridos e permitem concluir que espécies do gênero Erythroxylum dos estados do Rio Grande do Sul e de Santa Catarina, Sul do Brasil, demonstram importância tóxica, farmacológica e química, sendo parte destas influenciada pelo período de coleta, verão/ inverno. / “Chemical and Biological Study of Erythroxylum P. Browne Species Collected in Southern Brazil”. Erythroxylum P. Browne genus belongs to the Erythroxylaceae Kunth family and is mainly known due to E. coca and E. novogranatense species, the "coca plants". The genus is the only natural source of cocaine and other alkaloids with ecgonine nucleus, mainly responsible for the toxic and biological effects caused by the consumption of their species. The presence of cocaine is widely accepted for coca plants, but its biosynthesis by other species shows divergence, which may be related to the collect period. Besides these phytochemical peculiarities, the species of the genus also present important activities such as antioxidant and antimicrobial, besides toxicity to humans and sheep. Brazil is the center of diversity and endemism of the genus and in the south of the country, in the states of Rio Grande do Sul and Santa Catarina, the phytochemical characteristics, toxic and pharmacological potentials of the species present an open field for studies. Thus, phytochemical characteristics, toxic and pharmacological potentials of native species of the states of Rio Grande do Sul and Santa Catarina were assessed, collected in two distinct climatic periods, summer and winter, as well as a bibliographical review on cocaine producing species and implications under current Brazilian law. Some methodologies were used such as planaria, disc-diffusion in agar, microdilution in broth, extinction measurement of the absorption of cation 2,2-diphenyl-1-picrylhydrazyl and procedures recommended by the United Nations for the phytochemical investigation of cocaine producing species. It was verified that twenty-four species present the enzymatic apparatus for the production of cocaine. Although E. novogranatense originate income appropriate to traffic according to current Brazilian legislation, only E. coca is outlawed, which makes it necessary to include E. novogranatense in the list of proscribed plants. For the toxicological study developed with E. deciduum on planaria model, it was necessary to adapt the existing methodology. The extract of the species caused a significant increase in locomotion velocity (p= 0.016) and standardized stereotyped behaviors of type C position and screw- type hyperkinesia, characteristic events of dopaminergic neurotransmission in planarians. The results, besides expanding the possibilities of the use of these worms in search for active extracts, demonstrate that E. deciduum biosynthesizes active metabolites on this neurotransmitter, which may be related to the effects caused by the consumption of the plant species. The influence of the collect period on pharmacological potentials and phytochemical characteristics was investigated and the results demonstrate this influence. Different extracts of E. argentinum and E. deciduum collected during summer showed higher antimicrobial activity than the extracts obtained from winter collect. The ethanolic extract of E. argentinum, summer collect, may be considered a true antimicrobial, MIC= 0.78mg/ mL, on Staphylococcus aureus, and in this way it becomes a promising source for the discovery of new antimicrobial molecules. The extracts of E. argentinum and E. deciduum species demonstrate relevant results on antioxidant activity. The influence of the collecting period, summer/ winter, on the activity was verified. The influence of collect period on toxic- pharmacological activities is corroborated by the alkaloid profile obtained from nine species of the genus, collected during summer and winter in the states of Rio Grande do Sul and Santa Catarina. The alkaloid profile of E. amplifolium, E. argentinum, E. cuneifolium, E. cuspidifolium, E. deciduum, E. microphyllum, E. myrsinites, E. pelleterianum and E. vacciniifolium species shows the presence of alkaloids: ecgonidine methyl ester, ecgonine methyl ester, cuscohygrine and tropacocaine and the biosynthesis intermediates: hygrine, tropinone and tropanol. The identification of the ecgonine methyl ester and ecgonidine methyl ester also shows that Erythroxylum genus species present in southern Brazil have economic potential because they can be used in the production of toxicological standards. The aims were met and allow the conclusion that Erythroxylum genus of Rio Grande do Sul and Santa Catarina states, south of Brazil, show toxic, pharmacological and chemical importance, part of these being influenced by the collect period, summer/ winter.

Parmi les bio-polymères issus des ressources renouvelables, les polysaccharides fournissent une alternative intéressante aux polymères de synthèse. Dans ce contexte, l’objectif de ce travail de thèse est basé sur la conception des copolymères amphiphiles pour la préparation de nouveaux biomatériaux. Ainsi, l’hydroxypropylméthylcellulose (HPMC) a été étudiée en raison de ses propriétés remarquables, dont la biocompatibilité, la biodégradabilité, la rétention d'eau et la gélification thermoréversible. Ces propriétés sont utiles pour de nombreuses applications telles que le relargage de médicament, la préparation des membranes et la formation de biomatériaux. L'hydrolyse enzymatique avec des endo cellulases issues de Trichoderma reesei a été étudiée pour produire des fragments d'HPMC ayant une masse molaire (Mw) entre 6000 et 30000 g mol-1. Les paramètres de l’activité enzymatique ont été étudiés en fonction de : la nature de substrat, le temps de réaction et la concentration de l'enzyme. Les polymères obtenus ont été comparés à ceux produits par hydrolyse acide. Il a été constaté que la structure des polymères issus d’un procédé d’hydrolyse, varie en termes de degré de substitution pour un même Mw. Cet effet donne lieu à différentes propriétés de gélification thermoréversible. Des copolymères amphiphiles tels que HPMC-b-poly (propylène glycol) et HPMC-b-PLA ont été préparés par amination réductrice et par couplage click thiol-ene, respectivement. Les propriétés d’agrégation ont été caractérisées par la diffusion de la lumière (DLS), le microscope électronique en transmission (TEM) et par la séparation de phase obtenue par la mesure du point de trouble. / Following the concept of bio-refinery, we propose to produce small fragments of biopolymers that can be used further as building blocks to prepare novel polymeric architectures. In the case of polysaccharides, enzymatic hydrolysis enables to form reducing end groups after each cleavage on the polymer chain. Reaction by reductive amination affords the possibility to introduce polysaccharides fragments in a large variety of materials going from amphiphilic copolymers to more sophisticated devices. Hydroxypropyl methylcellulose (HPMC) was used in this work because of its remarkable properties including biocompatibility, biodegradability, water retention and thermoreversible gelation beneficial for many applications such as drug delivery, film and biomaterial formation. Enzymatic hydrolysis using endo cellulases from Trichoderma reesei was investigated to produce a library of HPMC fragments with molecular weight (Mw) from 6000 to 30000 g mol-1. Mw control was carried out by varying the procedure conditions including the nature of starting HPMC, reaction time and enzyme concentration. The obtained polymers were compared to those produced by acidic hydrolysis.According to the preparation conditions, the structure of short chain polymers regarding substitution degrees varied for the same Mw giving rise to different clouding temperature and thermoreversible gelation properties. Amphiphilic block copolymers HPMC-b-poly(propylene glycol) and HPMC-b-PLA were prepared by reductive amination and by the thiol-ene click reaction, respectively. Self-assembly properties of these novel block copolymer were characterized by dynamic light scattering (DLS), transmission electron microscope (TEM), and clouding point temperature.

Les polymères synthétiques sont largement utilisés aujourd’hui comme implants prothétiques. Malheureusement, ces implants sont invisibles en imagerie par résonance magnétique IRM. La visualisation de ces implants est une nécessité afin d'obtenir des informations concernant leur fixation dans le corps et leur situation post-opératoire.Un des défis est alors de fixer un agent de contraste sur l'implant médical. Pour cet objectif, un premier polymère va être fonctionnalisé avec un agent de contraste de manière covalente, puis on le dépose par enduction sur la surface de la prothèse. Les polymères seront fonctionnalisés par polymérisation radicalaire et par chimie "click". Dans une première étape, le poly(méthacrylate de méthyle-co-méthacrylate de propargyle) avec un faible rapport molaire en méthacrylate de propargyle (F <10%) est préparé par copolymérisation radicalaire du méthacrylate de méthyle et du méthacrylate de propargyle. Dans une deuxième étape, l'agent de contraste sera greffé avec par réaction de chimie « click » sur le poly(méthacrylate de méthyle) porteur de fonctions propargyles (PMMA-co-PMA). Sur ce squelette polymérique, un nouveau agent de contraste à base de gadolinium sera greffé. Le polymère obtenu sera déposé sur une maille de polypropylene commercial par la technique de l'aérographie et la maille sera évaluée pour l'IRM visualisation sur un7T instrument. Des tests de cytotoxicité et de cytocompatibilité seront effectuées pour évaluer l'utilisation de cet agent de contraste dans des applications biomédicales.En même temps, les techniques d'imagerie de fluorescence gagnent aussi en popularité . Pour cela, le même polymère synthétisé (PMMA–co-PMA) sera fonctionnalisé avec différents précurseurs fluorescents: anthracène , fluorescéine, complexe d’europium. / Synthetic polymers are widely used nowadays as prosthetic implants. Unfortunately, these implants are invsisble by magnetic resonance imaging (MRI). The visualization of these implants is a necessity in order to gain information concerning their fixation in the body and post-operation fate. One of the challenges is then to fix a contrast agent on the implant. Thus the objective is to develop novel strategies for the long-term visualization of prosthetic implants by MRI. For this goal, a polymer will first be functionalized with a contrast agent in a covalent way, and then it will be deposited by coating on the surface of the prosthesis. Polymers will be functionalized by free radical polymerization followed by “click chemistry. In a first step, poly(methyl methacrylate-co-propargyl methacrylate) with low molar ratio in propargyl methacrylate (F< 10 %) will be prepared by free radical copolymerization of methyl methacrylate with propargyl methacrylate. In a second step, a novel gadolinium based contrast agent will be grafted by click chemistry onto the propargylated poly(methyl methacrylate) (PMMA-co-PMA) polymer. The obtained polymeric contrast agent will be spread on a commercial polypropylene mesh by the airbrushing technique and the mesh will be assessed for MRI visualization on a 7T instrument. Cytocompatibility and cytotoxicity tests will be performed to evaluate the use of this contrast agent in biomedical applications.At the same time, fluorescence imaging techniques are also gaining popularity. For this, the same synthesized polymer (PMMA-co-PMA) will be attached to different fluorescent precursors: anthracene, fluoresceine, and europium complex.

Ketamine and phencyclidine (PCP) are noncompetitive antagonists of the N-methyl-D-aspartate (NMDA) type of ligand-gated glutamate receptors. Both agents have high abuse liability, and may produce dependence. Tolerance to the reinforcing effects of drugs of abuse is widely regarded as a key component of the dependence process. Therefore, the present study was conducted to examine whether tolerance develops to the reinforcing effects of ketamine, and whether PCP and dizocilpine, a noncompetitive NMDA antagonist with negligible abuse liability, produce cross-tolerance to the reinforcing effects of ketamine. Further, identification of the neural mechanisms that underlie tolerance to the reinforcing effects of drugs may yield information regarding drug dependence.

Tobacco SABP2, a 29. kDa protein catalyzes the conversion of methyl salicylic acid (MeSA) into salicylic acid (SA) to induce SAR. Pretreatment of plants with acibenzolar-. S-methyl (ASM), a functional analog of salicylic acid induces systemic acquired resistance (SAR). Data presented in this paper suggest that SABP2 catalyzes the conversion of ASM into acibenzolar to induce SAR. Transgenic SABP2-silenced tobacco plants when treated with ASM, fail to express PR-1 proteins and do not induce robust SAR expression. When treated with acibenzolar, full SAR is induced in SABP2-silenced plants. These results show that functional SABP2 is required for ASM-mediated induction of resistance.

Les protéines à « Methyl-CpG-binding domain » (MBD) jouent un rôle important dans l’interprétationde la méthylation de l’ADN conduisant à la répression transcriptionnelle via le recrutement decomplexes remodelant la chromatine. Dans les cancers, MBD2 jouerait un rôle essentiel dans la perted’expression des gènes hyperméthylés. Ainsi, MBD2 serait une cible potentielle pour rétablir, enpartie au moins, leur expression. Caractériser, à l’échelle du génome, la distribution de MBD2 et sesconséquences sur la répression transcriptionnelle au cours de la cancérogenèse est donc une étapeincontournable. (1) L’impact sur l’expression génique de l’inhibition de MBD2 par interférence àl’ARN, a été étudié en utilisant des puces, dans des cellules normales MRC5. La perte de MBD2n’induit pas de surexpression génique globale et la densité en CpG des promoteurs méthylés sembleêtre une composante importante dans la force de répression par MBD2. (2) Les profils de méthylationde l’ADN, de liaisons de MBD2 et de l’ARN polymérase II dans les cellules HeLa ont été analysés parChIP-on-chip avec des puces promoteurs. Ces mêmes approches couplées à l’analyse de l’acétylationdes histones H3 ont été réalisées dans un modèle cellulaire syngénique de progression tumoralemammaire humain. Dans les modèles étudiés, une forte proportion de gènes silencieux et méthylés estliée par MBD2. Les comparaisons entre cellules immortalisées et transformées ne montrent pas dechangements majeurs de la méthylation de l’ADN ou de la répression transcriptionnelle, par contreune redistribution de MBD2 parmi ces sites est observée, suggérant une redondance entre les protéinesliant l’ADN méthylé. / The Methyl-CpG-Binding Domain (MBD) proteins represent key molecules in the interpretation ofDNA methylation signals leading to gene silencing through recruitment of chromatin remodelingcomplexes. In cancer, a member of this protein family, MBD2, seems to play an important role in theloss of expression of aberrantly methylated genes. Thus, MBD2 may be a potential target toreestablish their expression. Mapping of MBD2 binding sites and the relationship between MBD2binding and transcriptional activity was, therefore, a crucial step. (1) We investigated the impact ofMBD2 inhibition by RNA interference on gene expression, using microarray analysis, in a normalhuman fibroblastic cell line, MRC-5. MBD2 depletion did not induce global gene overexpression andCpG density of the methylated promoters seems to be an important parameter in the strength of thetranscriptional repression mediated by MBD2. (2) Global profiling for different layers of epigeneticmodifications (DNA methylation, MBD2 association) and RNA polymerase II binding sites in HeLacells was analyzed by a ChIP-chip method using human promoter arrays. This approach, combinedwith an analysis of H3 histone acetylation patterns, was performed in a syngenic model of breastcancer progression. In the models analyzed MBD2 appeared to be a true methylation-dependenttranscriptional repressor. Furthermore, MBD2 binds to a high proportion of methylated silent genes.Comparisons between immortalized and transformed cells did not indicate major changes of DNAmethylation or gene silencing, while a redistribution of MBD2 among these sites was observed,suggesting a redundancy between methylated binding proteins.