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Time Dependent Mediators of HPA Activation Following Peripheral <i>E. coli</i> ChallengeZimomra, Zachary R. 26 July 2012 (has links)
No description available.
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Structural controls of Ni-Cu-PGE ores and mobilization of metals at the Garson Mine, SudburyMukwakwami, Joshua 31 July 2013 (has links)
The Garson Ni-Cu-PGE deposit is located on the South Range of the 1850 Ma Sudbury
structure along the contact between the Sudbury Igneous Complex (SIC) and the
underlying metasedimentary and metavolcanic rocks of the Paleoproterozoic Huronian
Supergroup. It comprises four ore bodies that are hosted by E-W-trending shear zones
that dip steeply to the south. The shear zones formed as south-directed D1 thrusts in
response to flexural-slip during regional buckling of the SIC. They imbricated the ore
zones, the SIC norite, the underlying Huronian rocks and they emplaced slivers of
Huronian rocks and anatectic breccia into the overlying Main Mass norite. Coexisting
garnet-amphibole pairs yielded syn-D1 amphibolite facies metamorphic temperatures
ranging from ~550°C to 590°C. The shear zones were coeval with the moderately southdipping
South Range and Thayer Lindsley shear zones, which formed to accommodate
the strain in the hinge zone as the SIC tightened with progressive D1 shortening. The SE
limb of the SIC was overturned together with the D1 thrusts, which were then reactivated
as steeply south-dipping reverse shear zones during syn-D2 greenschist metamorphism.
Syn-D2 metamorphic titanite yield a U-Pb age of ca. 1849 ± 6 Ma, suggesting that D1 and
D2 are part of a single progressive deformation event that occurred immediately after
crystallization of the SIC during the Penokean Orogeny.
The ore bodies plunge steeply to the south parallel to the colinear L1 and L2 stretching
mineral lineations. Ore types consist mainly of pyrrhotite-pentlandite-chalcopyrite breccia
ores, but also include pyrrhotite-pentlandite-chalcopyrite disseminated sulfide
mineralization in norite, and syn-D2 quartz-calcite-chalcopyrite-pyrrhotite-pentlandite
iv
veins. In the breccia ores, matrix sulfides surround silicate rock fragments that have a
strong shape-preferred orientation defining a pervasive foliation. The fragments are
highly stretched parallel to the mineral lineations in wall rocks, suggesting that the ore
bodies are zones of high strain. Pyrrhotite and chalcopyrite occur in piercement
structures, in boudin necks between fragments, in fractures in wall rocks and in fold
hinges, suggesting that the sulfides were mobilized by ductile plastic flow. Despite
evidence of high strain in the ore zones, the sulfide matrix in D1 and D2 breccia ores show
little evidence of strain as they consist predominantly of polygonal pyrrhotite aggregates,
suggesting that they recrystallized during, or immediately after D1 and D2. However, rare
elongate pyrrhotite grains aligned parallel to S2 are locally preserved only in D2 breccia
ores. Exsolution of pentlandite loops along grain boundaries of elongate pyrrhotite
formed S2-parallel pentlandite-rich layers in D2 breccia ores, whereas the pentlandite
loops are multi-oriented in D1 contact breccia as they were exsolved along grain
boundaries polygonal pyrrhotite. Because exsolution of pentlandite post-date D1 and D2,
and that individual pentlandite grains neither have a shape-preferred orientation nor show
evidence for cataclastic flow, the sulfides reverted to, and were mobilized as a
homogeneous metamorphic monosulfide solid solution (mss) during D1 and possibly D2.
This is in agreement with predictions from phase equilibria as the average Garson
composition plots within the mss field in Fe-Ni-S ternary diagram at temperatures above
~400°C.
Disseminated and breccia ores at Garson have similar mantle-normalized multi-element
chalcophile patterns as undeformed contact-type disseminated and massive ore,
v
respectively, at the well known Creighton mine in the South Range. This suggests that the
Garson ores are magmatic in origin and that their compositions were not significantly
altered by hydrothermal fluids and deformation. The lack of variations in Ni tenors
between the disseminated and breccias ores suggest that the R-factor was not the process
controlling metal tenors because the disseminated sulfides do not consistently have higher
metal tenors than the breccia ore. The breccia ores are enriched in Rh-Ru-Ir and are
depleted in Cu-Pd-Pt-Au, in contrast to footwall-type ore at the nearby Garson Ramp
mine which is enriched in the same metals. When Ni100, Rh100, Ir100, Pt100 and Pd100 are
plotted against Cu100, the breccia and footwall-type ore analyses plot along model mss
fractionation and sulfide melt model curves, suggesting that these two ore types are
related by mss fractionation.
In summary, the Garson breccia ores are mss cumulates that settled quickly at the base of
the SIC via a gravity filtration process, and were mobilized as a metamorphic mss by
ductile plastic flow during D1 and D2. Despite minor local hydrothermal mobilization of
some metals, the study confirms findings from other studies that highly deformed Ni-Cu-
PGE deposits, such as the Garson deposit, can provide important information on the
genesis of the deposits.
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STRUCTURAL CONTROLS OF Ni-Cu-PGE ORES AND MOBILIZATION OF METALS AT THE GARSON MINE, SUDBURYMukwakwami, Joshua 15 August 2013 (has links)
The Garson Ni-Cu-PGE deposit is located on the South Range of the 1850 Ma Sudbury
structure along the contact between the Sudbury Igneous Complex (SIC) and the
underlying metasedimentary and metavolcanic rocks of the Paleoproterozoic Huronian
Supergroup. It comprises four ore bodies that are hosted by E-W-trending shear zones
that dip steeply to the south. The shear zones formed as south-directed D1 thrusts in
response to flexural-slip during regional buckling of the SIC. They imbricated the ore
zones, the SIC norite, the underlying Huronian rocks and they emplaced slivers of
Huronian rocks and anatectic breccia into the overlying Main Mass norite. Coexisting
garnet-amphibole pairs yielded syn-D1 amphibolite facies metamorphic temperatures
ranging from ~550°C to 590°C. The shear zones were coeval with the moderately southdipping
South Range and Thayer Lindsley shear zones, which formed to accommodate
the strain in the hinge zone as the SIC tightened with progressive D1 shortening. The SE
limb of the SIC was overturned together with the D1 thrusts, which were then reactivated
as steeply south-dipping reverse shear zones during syn-D2 greenschist metamorphism.
Syn-D2 metamorphic titanite yield a U-Pb age of ca. 1849 ± 6 Ma, suggesting that D1 and
D2 are part of a single progressive deformation event that occurred immediately after
crystallization of the SIC during the Penokean Orogeny.
The ore bodies plunge steeply to the south parallel to the colinear L1 and L2 stretching
mineral lineations. Ore types consist mainly of pyrrhotite-pentlandite-chalcopyrite breccia
ores, but also include pyrrhotite-pentlandite-chalcopyrite disseminated sulfide
mineralization in norite, and syn-D2 quartz-calcite-chalcopyrite-pyrrhotite-pentlandite
iv
veins. In the breccia ores, matrix sulfides surround silicate rock fragments that have a
strong shape-preferred orientation defining a pervasive foliation. The fragments are
highly stretched parallel to the mineral lineations in wall rocks, suggesting that the ore
bodies are zones of high strain. Pyrrhotite and chalcopyrite occur in piercement
structures, in boudin necks between fragments, in fractures in wall rocks and in fold
hinges, suggesting that the sulfides were mobilized by ductile plastic flow. Despite
evidence of high strain in the ore zones, the sulfide matrix in D1 and D2 breccia ores show
little evidence of strain as they consist predominantly of polygonal pyrrhotite aggregates,
suggesting that they recrystallized during, or immediately after D1 and D2. However, rare
elongate pyrrhotite grains aligned parallel to S2 are locally preserved only in D2 breccia
ores. Exsolution of pentlandite loops along grain boundaries of elongate pyrrhotite
formed S2-parallel pentlandite-rich layers in D2 breccia ores, whereas the pentlandite
loops are multi-oriented in D1 contact breccia as they were exsolved along grain
boundaries polygonal pyrrhotite. Because exsolution of pentlandite post-date D1 and D2,
and that individual pentlandite grains neither have a shape-preferred orientation nor show
evidence for cataclastic flow, the sulfides reverted to, and were mobilized as a
homogeneous metamorphic monosulfide solid solution (mss) during D1 and possibly D2.
This is in agreement with predictions from phase equilibria as the average Garson
composition plots within the mss field in Fe-Ni-S ternary diagram at temperatures above
~400°C.
Disseminated and breccia ores at Garson have similar mantle-normalized multi-element
chalcophile patterns as undeformed contact-type disseminated and massive ore,
v
respectively, at the well known Creighton mine in the South Range. This suggests that the
Garson ores are magmatic in origin and that their compositions were not significantly
altered by hydrothermal fluids and deformation. The lack of variations in Ni tenors
between the disseminated and breccias ores suggest that the R-factor was not the process
controlling metal tenors because the disseminated sulfides do not consistently have higher
metal tenors than the breccia ore. The breccia ores are enriched in Rh-Ru-Ir and are
depleted in Cu-Pd-Pt-Au, in contrast to footwall-type ore at the nearby Garson Ramp
mine which is enriched in the same metals. When Ni100, Rh100, Ir100, Pt100 and Pd100 are
plotted against Cu100, the breccia and footwall-type ore analyses plot along model mss
fractionation and sulfide melt model curves, suggesting that these two ore types are
related by mss fractionation.
In summary, the Garson breccia ores are mss cumulates that settled quickly at the base of
the SIC via a gravity filtration process, and were mobilized as a metamorphic mss by
ductile plastic flow during D1 and D2. Despite minor local hydrothermal mobilization of
some metals, the study confirms findings from other studies that highly deformed Ni-Cu-
PGE deposits, such as the Garson deposit, can provide important information on the
genesis of the deposits.
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Investigation of Mantle Dynamics from Platinum Group Elements and Rhenium-Osmium Isotope Systematics of Mantle Xenoliths from OahuSen, Indra S 18 May 2010 (has links)
Intraplate volcanism that has created the Hawaiian-Emperor seamount chain is generally thought to be formed by a deep-seated mantle plume. While the idea of a Hawaiian plume has not met with substantial opposition, whether or not the Hawaiian plume shows any geochemical signal of receiving materials from the Earth’s Outer Core and how the plume may or may not be reacting with the overriding lithosphere remain debatable issues. In an effort to understand how the Hawaiian plume works I report on the first in-situ sulfides and bulk rock Platinum Group Element (PGE) concentrations, together with Os isotope ratios on well-characterized garnet pyroxenite xenoliths from the island of Oahu in Hawaii. The sulfides are Fe-Ni Monosulfide Solid Solution and show fractionated PGE patterns. Based on the major elements, Platinum Group Elements and experimental data I interpret the Hawaiian sulfides as an immiscible melt that separated from a melt similar to the Honolulu Volcanics (HV) alkali lavas at a pressure-temperature condition of 1530 ± 100OC and 3.1±0.6 GPa., i.e. near the base or slightly below the Pacific lithosphere. The 187Os/188Os ratios of the bulk rock vary from subchondritic to suprachondritic (0.123-0.164); and the 187Os/188Os ratio strongly correlates with major element, High Field Strength Element (HFSE), Rare Earth Element (REE) and PGE abundances. These correlations strongly suggest that PGE concentrations and Os isotope ratios reflect primary mantle processes. I interpret these correlations as the result of melt-mantle reaction at the base of the lithosphere: I suggest that the parental melt that crystallized the pyroxenites selectively picked up radiogenic Os from the grain boundary sulfides, while percolating through the Pacific lithosphere. Thus the sampled pyroxenites essentially represent crystallized melts from different stages of this melt-mantle reaction process at the base of the lithosphere. I further show that the relatively low Pt/Re ratios of the Hawaiian sulfides and the bulk rock pyroxenites suggest that, upon ageing, such pyroxenites plus their sulfides cannot generate the coupled 186Os-187Os isotope enrichments observed in Hawaiian lavas. Therefore, recycling of mantle sulfides of pyroxenitic parentage is unlikely to explain the enriched Pt-Re-Os isotope systematics of plume-derived lavas.
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Análise do transcriptoma durante a ontogenia do timo. / Analysis of the transcriptoma during the antogenia of the thymus.Magalhães, Danielle Aparecida Rosa de 10 May 2007 (has links)
O timo é um órgão complexo estruturado por um estroma, o qual é formado principalmente por células epiteliais corticais (cTECs) e por células epiteliais medulares (mTECs) além de outros tipos celulares como células dendríticas (DC), macrófagos, linfócitos B e fibroblastos. Além disso, os precursores das células T originados da medula óssea chegam ao timo (timócitos) se maturando em linfócitos T, os quais migram para a periferia. O timo é, portanto, o local de eventos muito importantes durante a maturação do sistema imune, incluindo o controle de sua própria homeostase. No presente estudo, procuramos retratar as principais características do timo por meio da análise da expressão gênica em grande escala, isto é, descrevendo parte de seu transcriptoma. Fizemos uso da tecnologia dos cDNA microarrays em duas versões. Na primeira delas utilizamos cDNA microarrays construídos em lâminas de vidro e sondas fluorescentes marcadas com fluorocromos Cy3 ou Cy5 e, na segunda versão utilizamos cDNA microarrays em membranas de náilon e sondas radioativas marcadas com o isótopo 33P. Para a análise dos dados, utilizamos programas de bioinformática dedicados, tais como o SAM (Significance analysis of microarrays) e o Cluster e TreeView. Três conjuntos de resultados foram possíveis. No primeiro conjunto observamos a ocorrência da expressão gênica promíscua (PGE) de antígenos de tecidos/órgãos parenquimatosos (TSAs), demarcando sua emergência temporal durante a ontogenia do timo murino, a qual é influenciada pelo background genético das linhagens isogênicas estudadas. A ocorrência da PGE no timo é associada às bases genético-moleculares da indução de tolerância imunológica nas células T, contribuindo com a prevenção da auto-imunidade. O segundo conjunto de resultados consistiu na análise da expressão gênica do timo de camundongos nocautes (KO) envolvendo genes importantes para a maturação das células T, tais como TCR?, LAT, Rel-b, RAG-1 e CD3?, possibilitando a observação de seus efeitos na regulação da transcrição neste órgão. Finalmente, o terceiro conjunto consistiu na definição da dissecação molecular virtual do timo. Por meio de perfis de expressão gênica particulares exibidos por cada tipo principal que povoa o timo, foi possível dissecar este órgão usando a tecnologia dos cDNA microarrays. / The thymus is a complex organ structured by a stroma, which is formed mainly by cortical epithelial cells (cTECs) and medullary epithelial cells (mTECs) besides of other cell types such as dendritic cells (DC), macrophages, B lymphocytes and fibroblasts. Moreover, the T cell precursors arising from the bone marrow reach the thymus (thymocytes) maturing in T lymphocytes, which migrate to the periphery. Thus, the thymus is the place of very important events during the maturation of the immune system, including the control of their own homeostasis. In the present study, we search to picture the main characteristics of the thymus by means of the large scale gene expression analysis that is, describing part of their transcriptome. We made use of the cDNA microarray technology in two versions. In the first one we used cDNA microarrays constructed on glass slides and fluorescent probes labeled with the fluorochromes Cy3 or Cy5 and in the second version we used cDNA microarrays on nylon membranes and radioactive probes labeled with 33P isotope. To data analysis we used dedicated bioinformatics programs, such as SAM (significance analysis of microarrays) and Cluster-Tree View. Three sets of results were possible. In the first set we observed the occurrence of the promiscuous gene expression (PGE) of parenchymal tissue/organ specific antigens (TSAs), demarking their temporal emergence during the murine thymus ontogeny, which is influenced by the genetic background of the inbred strains studied. The occurrence of PGE in the thymus is associated to the molecular-genetics basis of the immune tolerance of T cells, contributing with the prevention of autoimmunity. The second set of results consisted in the analysis of gene expression of thymus from knockout mice (KO) involving genes important for T cell maturation, such as TCR?, LAT, Relb, RAG-1 and CD3?, allowing the observation of its effects on the transcription regulation in this organ. Finally, the third set consisted in the definition of the virtual molecular dissection of the thymus. By means of particular gene expression profiling featured by each main cell type populating the thymus, it was possible to dissect this organ using the cDNA microarray technology.
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Análise do transcriptoma durante a ontogenia do timo. / Analysis of the transcriptoma during the antogenia of the thymus.Danielle Aparecida Rosa de Magalhães 10 May 2007 (has links)
O timo é um órgão complexo estruturado por um estroma, o qual é formado principalmente por células epiteliais corticais (cTECs) e por células epiteliais medulares (mTECs) além de outros tipos celulares como células dendríticas (DC), macrófagos, linfócitos B e fibroblastos. Além disso, os precursores das células T originados da medula óssea chegam ao timo (timócitos) se maturando em linfócitos T, os quais migram para a periferia. O timo é, portanto, o local de eventos muito importantes durante a maturação do sistema imune, incluindo o controle de sua própria homeostase. No presente estudo, procuramos retratar as principais características do timo por meio da análise da expressão gênica em grande escala, isto é, descrevendo parte de seu transcriptoma. Fizemos uso da tecnologia dos cDNA microarrays em duas versões. Na primeira delas utilizamos cDNA microarrays construídos em lâminas de vidro e sondas fluorescentes marcadas com fluorocromos Cy3 ou Cy5 e, na segunda versão utilizamos cDNA microarrays em membranas de náilon e sondas radioativas marcadas com o isótopo 33P. Para a análise dos dados, utilizamos programas de bioinformática dedicados, tais como o SAM (Significance analysis of microarrays) e o Cluster e TreeView. Três conjuntos de resultados foram possíveis. No primeiro conjunto observamos a ocorrência da expressão gênica promíscua (PGE) de antígenos de tecidos/órgãos parenquimatosos (TSAs), demarcando sua emergência temporal durante a ontogenia do timo murino, a qual é influenciada pelo background genético das linhagens isogênicas estudadas. A ocorrência da PGE no timo é associada às bases genético-moleculares da indução de tolerância imunológica nas células T, contribuindo com a prevenção da auto-imunidade. O segundo conjunto de resultados consistiu na análise da expressão gênica do timo de camundongos nocautes (KO) envolvendo genes importantes para a maturação das células T, tais como TCR?, LAT, Rel-b, RAG-1 e CD3?, possibilitando a observação de seus efeitos na regulação da transcrição neste órgão. Finalmente, o terceiro conjunto consistiu na definição da dissecação molecular virtual do timo. Por meio de perfis de expressão gênica particulares exibidos por cada tipo principal que povoa o timo, foi possível dissecar este órgão usando a tecnologia dos cDNA microarrays. / The thymus is a complex organ structured by a stroma, which is formed mainly by cortical epithelial cells (cTECs) and medullary epithelial cells (mTECs) besides of other cell types such as dendritic cells (DC), macrophages, B lymphocytes and fibroblasts. Moreover, the T cell precursors arising from the bone marrow reach the thymus (thymocytes) maturing in T lymphocytes, which migrate to the periphery. Thus, the thymus is the place of very important events during the maturation of the immune system, including the control of their own homeostasis. In the present study, we search to picture the main characteristics of the thymus by means of the large scale gene expression analysis that is, describing part of their transcriptome. We made use of the cDNA microarray technology in two versions. In the first one we used cDNA microarrays constructed on glass slides and fluorescent probes labeled with the fluorochromes Cy3 or Cy5 and in the second version we used cDNA microarrays on nylon membranes and radioactive probes labeled with 33P isotope. To data analysis we used dedicated bioinformatics programs, such as SAM (significance analysis of microarrays) and Cluster-Tree View. Three sets of results were possible. In the first set we observed the occurrence of the promiscuous gene expression (PGE) of parenchymal tissue/organ specific antigens (TSAs), demarking their temporal emergence during the murine thymus ontogeny, which is influenced by the genetic background of the inbred strains studied. The occurrence of PGE in the thymus is associated to the molecular-genetics basis of the immune tolerance of T cells, contributing with the prevention of autoimmunity. The second set of results consisted in the analysis of gene expression of thymus from knockout mice (KO) involving genes important for T cell maturation, such as TCR?, LAT, Relb, RAG-1 and CD3?, allowing the observation of its effects on the transcription regulation in this organ. Finally, the third set consisted in the definition of the virtual molecular dissection of the thymus. By means of particular gene expression profiling featured by each main cell type populating the thymus, it was possible to dissect this organ using the cDNA microarray technology.
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Modalités de contamination du ray-grass par les éléments du groupe platine et les hydrocarbures aromatiques polycycliques à proximité des voies routières / Contamination modalities of the ryegrass by the platinum group elements and the polycyclic aromatic hydrocarbons near the road waysTankari Dan-Badjo, Abdourahamane 31 January 2007 (has links)
Notre travail de thèse a porté sur les modalités de dépôts de PGE et HAP sur le fourrage à partir d’un bio-accumulateur (ray-grass). Les cinétiques du dépôt de PGE et HAP sur les plants de ray-grass exposé en bordure d’autoroute ont montré que l’essentiel de la contamination s’effectue durant les premières semaines d’exposition, et aussi que ces contaminants restent fixés au ray-grass au moins cinq semaines après son retrait de l’autoroute. L’étude de l’influence des conditions du trafic a montré un faible impact de l’autoroute sur la contamination du ray-grass en PGE et HAP par rapport à une route nationale, suggérant que le dépôt de PGE et HAP sur le ray-grass est beaucoup plus lié aux propriétés de leurs émissions par les véhicules que par le nombre de véhicules. La spatialisation de l’exposition du fourrage en PGE et HAP à l’échelle parcellaire a révélé une diminution significative des concentrations de Pd, Rh et HAP du ray-grass avec l’éloignement de la source d’émission. / Our thesis work concerned the methods of PGE and PAH deposits on fodder using a bio-accumulator (ryegrass). The deposit kinetics of PGE and PAH on ryegrass exposed in the vicinity of a highway showed that the main part of the contamination is carried out during the first weeks of exposure, and also that these contaminants remain fixed on the ryegrass at least five weeks after its removal from the highway. The study of the traffic conditions influence showed a weak impact of the highway on the ryegrass contamination by PGE and PAH compared to a rural road, suggesting that the PGE and PAH deposits on the ryegrass are much more related to the emission properties from the vehicles than to the number of vehicles. The spatialization of the fodder exposure in PGE and PAH on a fodder plot scale revealed a significant reduction of the Pd, Rh and PAH concentrations of the ryegrass with the distance of the emission source.
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Les monocytes CCR7+ comme outil de transport des nanoantirétroviraux vers le système nerveux centralLeblanc, David January 2015 (has links)
Actuellement, l'infection au virus de l'immunodéficience humaine de type 1 (VIH-1) est considérée comme une infection chronique contrôlable à moyen et long terme. En effet, l'utilisation appropriée de combinaisons d'antirétroviraux ainsi qu'un suivi du développement de la résistance chez le virus peut diminuer la charge virale pendant des décennies et retarder l'apparition du syndrome d'immunodéficience acquise (SIDA). Cependant, certains de ces médicaments, et tout particulièrement les inhibiteurs de protéase du VIH-1 pénètrent difficilement dans certains organes pouvant servir de réservoirs viraux comme c'est le cas pour le cerveau. Cette limitation favorise la persistance du virus permettant la réapparition rapide d'une forte virémie si les traitements sont interrompus. La réplication du VIH-1 dans le cerveau favorise le développement de déficits cognitifs, comportementaux et moteurs à long terme chez les personnes qui en sont atteintes. L'objectif principal de ce mémoire est de vérifier la possibilité d'utiliser les monocytes comme outil de transport des antirétroviraux sous forme de nanoparticules vers le réservoir du VIH-1 dans le système nerveux central (SNC). Cet objectif est vérifié à l'aide d'une reconstitution de la barrière hématoencéphalique (BHE), où la migration des monocytes chargés de nanoantirétroviraux est évaluée avec une lignée cellulaire monocytoïde, soit les Mono-Mac-1 (MM-1).
Des particules de tailles nanométriques dans lesquelles la ritonavir est encapsulée (nanoRTV) ont été développées afin de faciliter leur chargement à l'intérieur des cellules. Des essais de cytotoxicité ont montré que la ritonavir encapsulée n'était pas plus toxique que la ritonavir seule. Par la suite, la capacité de chargement, de rétention ainsi que de relâchement de nanoRTV ont été mesurés dans le temps avec les cellules MM-1. Les résultats démontrent que les cellules MM-1 sont tout à fait capables de stocker des quantités importantes de ritonavir et de garder près de 40 % de la quantité initialement chargée sur une période de sept jours.
Les essais de migration à travers la BHE reconstituée indiquent que les MM-1 chargées avec la nanoRTV perdent plus de la moitié de leur capacité de migration à travers la BHE en présence de chimiokines. Cependant, la pré-stimulation des cellules à la PGE[indice inférieur 2] avant le chargement des nanoRTV semble rétablir la capacité de la migration à travers cette barrière.
Cette étude est complémentaire à d'autres travaux de recherche visant l'utilisation de cellules comme outil de transport pour la livraison de médicaments à des sites anatomiques ciblés. De plus, nos résultats suggèrent que les monocytes pourraient être des acteurs importants dans ce type de thérapie, étant des cellules avec une forte capacité de migration à travers la BHE.
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Modulation de l'expression du récepteur CCR7 chez les monocytes: Impact de l'activation de LXR∝ et de la prostaglandine E[indice inférieur 2]Tanné, Bérengère January 2015 (has links)
Les maladies cardiovasculaires étant la première cause de mortalité au monde depuis une quinzaine d’années, de nombreuses recherches ont vu le jour sur plusieurs récepteurs impliqués dans ces maladies. C’est le cas du récepteur « Liver X Receptor », un récepteur nucléaire responsable du maintien de l’homéostasie du cholestérol et du glucose ainsi que du contrôle de l’inflammation. Les travaux réalisés dans le cadre de cette maîtrise avaient pour objectifs de mieux comprendre les éléments immunologiques et moléculaires contrôlant la migration des monocytes humains. Tout d’abord, nous avons déterminé le rôle de la prostaglandine E[indice inférieur 2], une cytokine produite massivement en inflammation, en combinaison avec l’activation du récepteur « Liver X Receptor », dans le contrôle de l’expression du récepteur de chimiokine CCR7 chez les monocytes. Ce récepteur est responsable de la migration des leucocytes vers les ganglions lymphatiques sous l’action chimiotactique des chimiokines CCL19 et CCL21. Nous avons démontré que la prostaglandine E[indice inférieur 2] en combinaison avec l’activation du récepteur « Liver X Receptor » induit la transcription de l’ARNm de CCR7 chez les monocytes et leur migration subséquente vers les chimiokines CCL19 et CCL21. Cependant, cette augmentation de la capacité migratoire n’est pas corrélée avec une augmentation de l’expression protéique de CCR7. Nous avons également observé que la prostaglandine E[indice inférieur 2] cause une diminution importante de l’expression de ABCG1, l’un des gènes cibles du récepteur « Liver X Receptor » impliqué dans le relargage du cholestérol. L’importance des récepteurs EP[indice inférieur 2] et EP[indice inférieur 4] a été démontré dans l’expression de l’ARNm et la fonctionnalité de CCR7. La prostaglandine E[indice inférieur 2] semble lier préférentiellement le récepteur EP[indice inférieur 4] plutôt que le récepteur EP[indice inférieur 2]. De plus, l’importance de la voie de signalisation induite par PI3K dans la modulation de la capacité migratoire a également été démontrée. Ces travaux ont permis de mettre en lumière les principaux acteurs moléculaires impliqué dans la migration des monocytes suite à l’activation du récepteur « Liver X Receptor » en présence de la prostaglandine E[indice inférieur 2].
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Accumulation of platinum group elements by the marine microalga, Chlorella stigmatophoraShams, Leyla January 2010 (has links)
Very little information exists on the marine biogeochemistry of Rh, Pd and Pt, or the platinum group elements (PGE), an emerging group of contaminants whose principal emissions are associated with the abrasion of the catalytic converter in motor vehicles and chemotherapy drugs discharged in hospital wastes. In this study, Rh(III), Pd(II) and Pt(IV) were added individually and in combination to cultures of the marine microalga, Chlorella stigmatophora, maintained in coastal seawater at 15oC and under fluorescence lighting both in the presence and absence of trace nutrients (e.g. Fe, Co, Zn and EDTA). The accumulation of PGE was established under varying conditions (pH, algal biomass, PGE concentration, time) by ICP-MS analysis of seawater and nitric acid digests and EDTA washes of the alga, the latter giving a measure of PGE adsorption by C. stigmatophora. Under all conditions the extent of accumulation was in the order: Rh > Pd >> Pt. In short-term (24-h) exposures, accumulation isotherms were quasi-linear up to PGE concentrations of 30 ug L-1, although Pd displayed convexity, hence saturation of available binding sites, at greater concentrations. The pH, adjusted between about 5.5 and 9.5 by addition of acid or base, did not have a great impact on PGE accumulation, with Rh displaying a moderate increase in accumulation and Pd a moderate reduction with increasing pH. More important, all PGE displayed a significant reduction in accumulation on a weight-normalized basis with increasing concentration of algae, an effect not reported for metal-marine algal interactions previously in the literature. Longer-term experiments showed that the rates of both overall accumulation and internalization were greatest for Pd and least for Pt. Consistent with this observation, the toxicity to C. stigmatophora evaluated by both pigment content and growth rate, was significantly greater for Pd than for Pt. Differences in the biogeochemical behaviours among the PGE are attributed to differences in their aqueous speciation in seawater, different affinities for the algal surface, different tendencies to cross the cell membrane, and especially with regard to Pd and Pt, differences in the rates of these interactions. Thus, although the equilibrium chemistries of Pd and Pt are very similar, their differential biogeochemistries are the result of kinetic constraints on reactions involving the latter. Because the environmental concentrations of PGE are predicted to increase with increasing emissions from vehicles and hospitals, the results of this study make an important contribution to an improved understanding of the likely effects and fates of these emerging contaminants in the marine environment. The results are also more generally important to an improved understanding of the interactions of trace metals with microalgae in seawater.
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