Bis-locked nucleic acids : a new tool for double helix invasion

Deoxyribonucleic acid (DNA) is a macromolecule that contains the information for all living organisms to achieve important cellular processes such as growth and replication. DNA consists of two strands coiled around each other to form a double helix. Several interactions including Watson-Crick pairing and stacking between the bases stabilize the double helix. To ensure the integrity of genetic information, the bases are on the inside the double helix whereas the phosphate and sugar groups are on the outside. Thus, most DNA information is not accessible until DNA is unwound prior to replication or transcription. In cells, enzymes called helicases achieve DNA strands separation. The anti-gene strategy aims to introduce a short single-stranded oligonucleotide (ON) to bind genomic DNA at a specific site to block the mRNA transcription. As a result, mRNA and protein expression for a specific gene are expected to be reduced, which could be beneficial in certain clinical contexts. However, this therapeutic strategy is hampered by the low stability of the DNA binding, the difficulty to reach the genomic target and to block the RNA polymerase, suggesting the needs for new DNA binding ONs. In this thesis, we developed clamp-ONs, bis-locked nucleic (bisLNAs), binding via Hoogsteen and Watson-Crick interactions. In paper I, we assessed their binding characteristics and demonstrated their ability to invade supercoiled DNA at intranuclear pH and salt conditions. In paper II, we investigated the step-by-step mechanism for bisLNA invasion. Based on this mechanism, we designed a new generation of bisLNAs using nonnatural modifications such as a stacking linker and 2´-glycylamino LNAs. In paper III, we investigated how the bisLNAs invade in a more complex environment using rolling circle amplification for detection

¿Quién necesita una lengua? Política y planificación lingüística en el departamento del Cauca

El propósito de este artículo es realizar una reflexión acerca de la forma en la cual las motivaciones políticas que trazan los límites y condiciones de la planificación lingüística hoy, se establecen en relación con las políticas de reconocimiento y administración de la diversidad cultural y lingüística por parte del estado colombiano. Para este fin me centraré en el caso del proceso de fortalecimiento de lengua nam trik o namuy wam, hablada en el departamento del Cauca

El proceso de adopción en Colombia

La incertidumbre de la sociedad ante en el proceso de Adopción en Colombia lleva al Instituto Colombiano de Bienestar Familiar replantee las normas, lineamientos, requisitos entre otros, con el fin de beneficiar a los NNA; sin embargo la realidad que se afronta dentro y fuera del país en la Adopción es crítica y debido a los continuos desfalcos a los que se ven sometidas las familias desesperadas con interés de adoptar; muchos son los testigos pero a pocos se les hace justicia; el ICBF, con pocas herramientas seguirá tratando de mejorar y de brindar ayudas que fortalezcan el proceso de Adopción en Colombia.La incertidumbre de la sociedad ante en el proceso de Adopción en Colombia lleva al Instituto Colombiano de Bienestar Familiar replantee las normas, lineamientos, requisitos entre otros, con el fin de beneficiar a los NNA; sin embargo la realidad que se afronta dentro y fuera del país en la Adopción es crítica y debido a los continuos desfalcos a los que se ven sometidas las familias desesperadas con interés de adoptar; muchos son los testigos pero a pocos se les hace justicia; el ICBF, con pocas herramientas seguirá tratando de mejorar y de brindar ayudas que fortalezcan el proceso de Adopción en Colombia

Influence of wood component on physical and chemical transformations during high temperature heating of composite fuel based on bituminous coal

Experimental studies of ignition delay time for mixtures of dispersed hard coal of two types and milled wood over a wide temperature range have been performed. Time of total completion of organic part pyrolysis of both components at different concentrations have been established in order to assess the prospects for such fuels application in large- and small-scale power engineering (combustion in boiler furnaces of different capacities). It has been established that simultaneous thermal decomposition of mixture of coal and wood particles leads to a significant change of pyrolysis temperature range and release of anthropogenic gases (sulfur and nitrogen oxides) in case of high-temperature heating of the mixture based on lean coal. The same effect, but in much smaller scale, has been recorded for a mixture based on long-flame coal. A hypothesis has been formulated on the mechanism of sulfur and nitrogen oxides precipitation during thermal decomposition of the mixture of lean coal and wood particles as a result of interaction between transitory gaseous and solid pyrolysis products of coal and wood in the temperature range up to 1000°C. Prospects of applying the milled coal and wood mixtures as fuel for steam and hot water boilers have been substantiated. With a small decrease of energy characteristics of such fuels, compared to homogeneous coals, significant improvement of ecological and economic characteristics of the fuel combustion processes can be achieved. It has been shown that vital synergistic effect of co-combustion of coal and wood particles is achieved only with certain coals

El auditor interno y su independencia

El estudio realizado tuvo como objetivo general, el analizar la independencia del auditor, debido a que su contratación depende de lo que disponga el representante legal de la compañía que auditan. El soporte que se tuvo para este análisis fue con base en lo observado en la ley 87 de 1993 y otros artículos de internet donde se relaciona ejemplos de fraudes que ponen en tela de juicio la confianza del auditor. La metodología utilizada es sencilla entendible, donde resulta argumentando las posibles soluciones de contratación que facilita la imparcialidad de los auditores en los dictámenes e informes que emiten. Para la recopilación de la información se utilizó el Internet como herramienta de investigación y consulta, facilitando de esta manera un enfoque argumentativo al ensayo

A poética de Kokin Wakashü

Tradução do Prefácio da antologia poética Kokin Wakashü, escrito pelo seu organizador Kino Tsurayuki, onde se encontra exposta a poética aristocrática japonesa do início do século X, à qual foram acrescidas breves considerações.Translation of the Kokin wakashü preface’s, written by its organizer KinoTsurayuki in which he exposes a briefing of Japanese aristocratic poetics in early Xth century, followed by a short analysis

Recherche d'inhibiteurs naturels des protéines anti-apoptotiques Bcl-xL et Mcl-1

In order to search for natural inhibitors of anti-Apoptotic protein Bcl-XL and Mcl-1, two bioassays were developed on Bcl-XL/Bak-CF and Mcl-1/Bid-CF. Both assays use fluorescent polarisation, and are based on binding of a fluorescein labeled pro-Apoptotic peptide (Bak-CF or-CF Bid) with an anti-Apoptotic protein (Bcl-XL or Mcl-1). Nearly 600 extracts from various parts of the world were screened on both Bcl-XL and Mcl-1 proteins to select the ethyl acetate bark extracts of Knema hookeriana (Myristicaceae) and Fissistigma latifolium (Annonaceae). The chemical analysis of the constituents of K. hookeriana has led to the isolation of 12 phenolic lipids. 6 of them were never isolated from a living organism. Only anacardic acids showed very strong inhibition of the interaction Bcl-XL/Bak-CF and Mcl-1/Bid-CF in fluorescent polarisation assays. Further study of the interactions between the most active anacardic acid and proteins (Bcl-XL, Mcl-1, Bak and Bid) by NMR showed that the modulation of Bcl-XL/Bak and Mcl-1/Bid is not related to the affinity of the compoun to the anti-Apoptotic proteins, Bcl-XL and Mcl-1 but to its affinity for peptides, Bid and Bak. The bioguided fractionation of the AcOEt bark extract of F. latifolium led to the isolation of a novel prenylated chalcone, (±)-Écarlottone having a dual activity on protein, Bcl-XL and Mcl-1. Subsequently, fractionation "NMR-Guided" led to the isolation of 6 new analogs.Dans le but de rechercher des inhibiteurs naturels des protéines anti-Apoptotiques Bcl-XL et Mcl-1, deux essais biologiques ont été mis au point sur Bcl-XL/Bak-CF et Mcl-1/Bid-CF. Ces deux tests utilisent la polarisation de fluorescence et sont basés sur la liaison d’un peptide pro-Apoptotique marqué à la fluorescéine (Bak-CF ou Bid-CF) avec une protéine anti-Apoptotique (Bcl-XL ou Mcl-1). Au total, près de 600 extraits de pantes, provenant de diverses régions du monde, ont été criblés sur les deux protéines Bcl-XL et Mcl-1 permettant de sélectionner les extraits acétate d’éthyle des écorces de Knema hookeriana (Myristicaceae) et de Fissistigma latifolium (Annonaceae). L’analyse chimique des constituants des écorces de K. hookeriana a conduit à l’isolement de 12 lipides phénoliques dont 6 n’avaient jamais été isolés d’un organisme vivant. Seuls les acides anacardiques ont révélé de très fortes inhibitions de l’interaction Bcl-XL/Bak-CF et Mcl-1/Bid-CF dans les essais par polarisation de fluorescence. Une étude plus approfondie des interactions entre le plus actif des produits et les protéines (Bcl-XL, Mcl-1, Bak et Bid) par RMN, a montré que la modulation des interactions Bcl-XL/Bak et Mcl-1/Bid n’est pas liée à l’affinité de l’acide anacardique pour les protéines Bcl-XL et Mcl-1 mais a une forte affinité pour les peptides Bid et Bak. Le fractionnement bioguidé de l’extrait AcOEt des écorces de F. latifolium a conduit à l’isolement d’une nouvelle chalcone prénylée, la (±)-Écarlottone possédant une dual activité sur les protéines, Bcl-XL et Mcl-1. Par la suite, le fractionnement "RMN-Guidé" a mené à l’isolement de 6 analogues