Genomweite Bemühungen haben eine große Anzahl langer nichtkodierender RNAs (lncRNAs) identifiziert, obwohl ihre möglichen Funktionen weitgehend rätselhaft bleiben. Hier verwendeten wir ein System zur synchronisierten Blüteninduktion in Arabidopsis, um 4106 blütenbezogene lange intergene RNAs (lincRNAs) zu identifizieren. Blütenbezogene lincRNAs sind typischerweise mit funktionellen Enhancern assoziiert, die bidirektional transkribiert werden und mit verschiedenen funktionellen Genmodulen assoziiert sind, die mit der Entwicklung von Blütenorganen zusammenhängen, die durch Koexpressionsnetzwerkanalyse aufgedeckt wurden. Die Master-regulatorischen Transkriptionsfaktoren (TFs) APETALA1 (AP1) und SEPALLATA3 (SEP3) binden an lincRNA-assoziierte Enhancer. Die Bindung dieser TFs korreliert mit der Zunahme der lincRNA-Transkription und fördert möglicherweise die Zugänglichkeit von Chromatin an Enhancern, gefolgt von der Aktivierung einer Untergruppe von Zielgenen. Darüber hinaus ist die Evolutionsdynamik von lincRNAs in Pflanzen, einschließlich nicht blühender Pflanzen, noch nicht bekannt, und das Expressionsmuster in verschiedenen Pflanzenarten war ziemlich unbekannt. Hier identifizierten wir Tausende von lincRNAs in 26 Pflanzenarten, einschließlich nicht blühender Pflanzen. Ein direkter Vergleich von lincRNAs zeigt, dass die meisten lincRNAs speziesspezifisch sind und das Expressionsmuster von lincRNAs einen hohen Transkriptionsumsatz nahe legt. Darüber hinaus zeigen konservierte lincRNAs eine aktive Regulation durch Transkriptionsfaktoren wie AP1 und SEP3. Konservierte lincRNAs zeigen eine konservierte blütenbezogene Funktionalität sowohl in der Brassicaceae- als auch in der Grasfamilie. Die Evolutionslandschaft von lincRNAs in Pflanzen liefert wichtige Einblicke in die Erhaltung und Funktionalität von lincRNAs. / Genome-wide efforts have identified a large number of long non-coding RNAs (lncRNAs), although their potential functions remain largely enigmatic. Here, we used a system for synchronized floral induction in Arabidopsis to identify 4106 flower-related long intergenic RNAs (lincRNAs). Flower-related lincRNAs are typically associated with functional enhancers which are bi-directionally transcribed and are associated with diverse functional gene modules related to floral organ development revealed by co-expression network analysis. The master regulatory transcription factors (TFs) APETALA1 (AP1) and SEPALLATA3 (SEP3) bind to lincRNA-associated enhancers. The binding of these TFs is correlated with the increase in lincRNA transcription and potentially promotes chromatin accessibility at enhancers, followed by activation of a subset of target genes. Furthermore, the evolutionary dynamics of lincRNAs in plants including non-flowering plants still remain to be elusive and the expression pattern in different plant species was quite unknown. Here, we identified thousands of lincRNAs in 26 plant species including non-flowering plants, and allow us to infer sequence conserved and synteny based homolog lincRNAs, and explore conserved characteristics of lincRNAs during plants evolution. Direct comparison of lincRNAs reveals most lincRNAs are species-specific and the expression pattern of lincRNAs suggests their high evolutionary gain and loss. Moreover, conserved lincRNAs show active regulation by transcriptional factors such as AP1 and SEP3. Conserved lincRNAs demonstrate conserved flower related functionality in both the Brassicaceae and grass family. The evolutionary landscape of lincRNAs in plants provide important insights into the conservation and functionality of lincRNAs.

This work deals with the transmittance of a family of non-steroidal anti-inflammatory drugs across biological membranes in combination with the use of hyaluronan. Hyaluronic acid (hyaluronan, HYA) is a linear polysaccharide formed from disacharide units containing N-acetyl-D-glucosamine and glucuronic acid. HYA is present in almost all biological fluids and tissues, so there is an assumption that could affect the penetration of substances through the skin. Standards were prepared by anti-inflammatory drugs in admixture with various concentrations hyaluronan and subsequently measured transmittance of such substances through the skin. Standards were applied to the skin obtained from pig auricle. The drug content was determined by HPLC.

Chez l’embryon précoce, une vague de reprogrammation majeure survient et permet de réinitialiser les profils de méthylation d’ADN de l’ensemble du génome. Lors de cette reprogrammation, les régions différentiellement méthylées (DMRs) (i.e., gènes empreintes) doivent toutefois être protégées de la déméthylation par une action continue de DNMT1 (Méthyltransférase d’ADN 1) pour assurer le développement adéquat de l’épigénome du fœtus. Sachant que l’induction d’une perte temporaire d’expression de Dnmt1 dans un modèle de cellules souches embryonnaires de souris entraîne la perte permanente des patrons de méthylation d’ADN aux régions DMRs et DMR-like, mon projet de recherche vise à comprendre pourquoi ces régions sont incapables de retrouver leurs patrons de méthylation d’ADN initiaux. Notre hypothèse est qu’une adaptation épigénétique (i.e. réarrangement erroné de certaines modifications d’histones) survient aux régions régulatrices de l’expression des gènes (promoteurs et enhancers) et empêche directement ou indirectement le retour au paysage épigénétique initial aux régions affectées. L’objectif du projet est donc de précisément définir comment la perte temporaire de Dnmt1 remodèle le paysage épigénétique aux régions promotrices (H3K4me3, H3K27me3, H3K27ac, H3K4me1, H3K9me3, méthylation d’ADN) et comment les adaptations épigénétiques sont associées avec des changements de l’expression des gènes (ex : gènes des régions DMRs et DMRs-like). / In early embryos, a major reprogramming wave occurs and permits to reset DNA methylation profiles genome-wide. During the reprogramming wave, differentially methylated regions (DMRs) (imprinted genes) must be protected from demethylation by the continuous action of DNMT1 (DNA Methyltransferase 1) to ensure the proper development of the foetal epigenome. As the induction of a temporary loss of Dnmt1 expression in a mouse embryonic stem cell model leads to permanent losses of DNA methylation at DMR and DMR-like regions, my project aims to understand why those regions are unable to re-establish their initial DNA methylation patterns. Our hypothesis is that an epigenetic adaptation (erroneous rearrangement of certain histone modifications) occurs at regulatory regions controlling gene expression (promoters and enhancers) and impede directly or indirectly the affected regions to return to their initial epigenetic landscape. The goal of this project is thus to define how the temporary loss of Dnmt1 remodels the epigenetic landscape at promoter regions (H3K4me3, H3K27me3, H3K27ac, H3K4me1, H3K9me3, DNA methylation) and how the epigenetic adaptations are associated with changes in gene expression (ex: genes in DMR and DMR-like regions).

No description available.

Cetoconazol é um fármaco antimicótico largamente utilizado e veiculado por diversas formas farmacêuticas. Apesar de ser comprovadamente eficaz, é uma substância muito hepatotóxica quando administrado por via oral. Por esse motivo justifica-se o seu emprego em preparações tópicas e sistemas transdérmicos. Essa substância apresenta razoáveis níveis de penetração elou permeação cutânea, mas esses níveis podem ser melhorados através da incorporação, às formulações, de substâncias denominadas promotores de permeação/penetração (enhancers). Essas substâncias têm a função de modificar a difusão dos fármacos através da pele. Neste trabalho, foi estudada a liberação/permeação do cetoconazol de cremes O/A contendo os promotores de permeação/penetração, propilenoglicol e uma solução alcóolica de mentol, empregados em associação e isoladamente na concentração de 0 a 5% p/p. O estudo foi conduzido in vitro, utilizando célula de Franz modificada com o emprego de membrana sintética de acetato de celulose. Foram preparadas e testadas dez formulações, a partir de uma fórmula de creme O/A não-iônico. Dentre as dez formulações estudadas aquela que apresentou melhores resultados quanto aos parâmetros de fluxo e coeficiente de permeabilidade, após uma hora do início do experimento, foi uma formulação que apresenta 1% p/p de propilenoglicol e 1% p/p de solução alcoólica de mentol. / Ketoconazole is an antifungal drug and is largely employed in many delivery systems and dosage forms. Oral administration is not recommended because of its hepatotoxic effects, so topical preparations are employed. This drug shows skin penetration and/or permeation levels, but these levels may be enhanced by the addition of enhancers. These substances modify the diffusion of drugs through skin. In this work, the liberation/permeation of ketoconazole from, O/W creams was studied. These creams have propylene glycol and na alcoholic menthol solution as enhancers, in a range from 0 to 5%w/w. It was an in-vitro experiment, employing Franz modified cells and synthetic cellulose membrane Ten nonionic O/W creams were made and tested. Among the ten tested formulations the one which showed best results in flux and permeability coefficient, after 1 hour, was a formulation which has 1 % w/w of menthol alcoholic solution concentrations.

Cetoconazol é um fármaco antimicótico largamente utilizado e veiculado por diversas formas farmacêuticas. Apesar de ser comprovadamente eficaz, é uma substância muito hepatotóxica quando administrado por via oral. Por esse motivo justifica-se o seu emprego em preparações tópicas e sistemas transdérmicos. Essa substância apresenta razoáveis níveis de penetração elou permeação cutânea, mas esses níveis podem ser melhorados através da incorporação, às formulações, de substâncias denominadas promotores de permeação/penetração (enhancers). Essas substâncias têm a função de modificar a difusão dos fármacos através da pele. Neste trabalho, foi estudada a liberação/permeação do cetoconazol de cremes O/A contendo os promotores de permeação/penetração, propilenoglicol e uma solução alcóolica de mentol, empregados em associação e isoladamente na concentração de 0 a 5% p/p. O estudo foi conduzido in vitro, utilizando célula de Franz modificada com o emprego de membrana sintética de acetato de celulose. Foram preparadas e testadas dez formulações, a partir de uma fórmula de creme O/A não-iônico. Dentre as dez formulações estudadas aquela que apresentou melhores resultados quanto aos parâmetros de fluxo e coeficiente de permeabilidade, após uma hora do início do experimento, foi uma formulação que apresenta 1% p/p de propilenoglicol e 1% p/p de solução alcoólica de mentol. / Ketoconazole is an antifungal drug and is largely employed in many delivery systems and dosage forms. Oral administration is not recommended because of its hepatotoxic effects, so topical preparations are employed. This drug shows skin penetration and/or permeation levels, but these levels may be enhanced by the addition of enhancers. These substances modify the diffusion of drugs through skin. In this work, the liberation/permeation of ketoconazole from, O/W creams was studied. These creams have propylene glycol and na alcoholic menthol solution as enhancers, in a range from 0 to 5%w/w. It was an in-vitro experiment, employing Franz modified cells and synthetic cellulose membrane Ten nonionic O/W creams were made and tested. Among the ten tested formulations the one which showed best results in flux and permeability coefficient, after 1 hour, was a formulation which has 1 % w/w of menthol alcoholic solution concentrations.

Living cells accumulate compensatory solutes for protection against the harmful effects of extreme environmental conditions such as high salinity, temperature and desiccation. Even at high concentrations these solutes do not disrupt the normal cellular functions and at times counteract by stabilizing the cellular components. These properties of compensatory solutes have been exploited for stabilizing proteins and cells in vitro. Betaines are widespread natural compensatory solutes that have also been used in other applications such as therapeutic agents and polymerase chain reaction (PCR) enhancers. Some biomedical applications of novel synthetic analogues of natural betaines were investigated. Natural compensatory solutes are either dipolar zwitterionic compounds or polyhydroxyl compounds, and the physical basis of compensation may differ between these, so one focus was on synthetic betaines with hydroxyl substituents. The majority of the synthetic solutes stabilized different model proteins against stress factors such as high and low temperatures. The presence of hydroxyl groups improved protection against desiccation. The observed stabilization effect is not just on the catalytic activity of the enzyme, but also on its structural conformation. Synthetic compensatory solutes have a potential application as protein stabilizers. Dimethylthetin was evaluated as a therapeutic agent and found to be harmful in a sheep model. However, from the study we were able to generate a large-animal continuous ambulatory peritoneal dialysis (CAPD) model and showed that glycine betaine could be added to the dialysis fluid in chronic renal failure. Some synthetic compensatory solutes reduce the melting temperatures of DNA better than most natural solutes. Synthetic solutes were identified that have potential to enhance PCR and could replace some reagents marketed by commercial suppliers. Density, viscosity and molecular model data on the solutes showed correlations with the biochemical effects of the solutes, but no physical measurements were found that reliably predicted their potential for biotechnological applications.

No description available.