International Journal of Global Community (Riksawan Institute - IJGC-RI)
Not a member yet
12510 research outputs found
Sort by
Gene delivery with cationic lipids:fundamentals and potential applications
No full textPrinciple of gene therapy.Although the objectives and principles of gene therapy have been well-defined over the last decades, its application as a versatile, therapeutically successful approach has not yet met expectations. At the onset, the primary goal of gene therapy was to replace a deficient gene in a genetically inherited disease with a normal copy, thereby restoring production of a functional protein. Soon afterwards, this goal was extended to include genetic defects beyond inherited disorders, since modulation of the regulation of gene expression was also involved in numerous acquired diseases. The potential of gene therapy for therapeutic applications thereby grew with the comprehension of mechanisms of diseases and the implication of genes in these events. Nowadays, it is clear that gene therapy not only may lead to its primary goal of replacing a deficient gene, but it could also lead to a modulation of the expression of genes acting on the physiology of malignant cells. Furthermore, by means of gene therapy, functions might be integrated into cells that are not originally present and that could serve a therapeutic purpose. Thus in a modern concept, gene therapy refers to the potential use of nucleic acids, irrespective of whether it concerns plasmid DNA, antisense oligonucleotides or siRNA, to modulate in any kind of way the expression of genes in cells for therapeutic purposes.Viral and non-viral gene delivery.Depending on the vectors used for nucleic acid transfer, gene delivery is roughly divided into two main categories: viral and non-viral gene delivery. The first vectors developed were based on using viruses or pseudo-viral particles, exploiting their ability to penetrate the cell for intracellular delivery of their genome in order to use the host machinery for the production of viral proteins. Because of their immunogenicity and potential oncogenicity, possibly resulting from mutational insertion defects when the viral genome integrates into the host genome, viral vectors may pose serious problems in terms of safety, thus jeopardizing their use as therapeutic drugs. Cationic lipids and cationic polymers can be used as well to complex nucleic acids, thereby forming so-called lipoplexes and polyplexes, respectively, and these complexes have been shown to similarly deliver genes into the cells. As opposed to the viral vectors, these systems are collectively known as non-viral gene delivery systems. Moreover because they are immunologically inert these vectors are thought to be safer in vivo. In contrast to viral particles they are not limited to the delivery of coding nucleic acids but can accommodate a greater variety of cargo, including antisense ODNs, siRNAs and entire genes. Finally, non-viral vectors are easier to produce and better amenable to chemical modifications for the purpose of effectuating therapeutic applications. However the major drawback of non-viral vectors is a lower efficiency in transfection, especially in vivo, that hinders their use for in vivo therapeutic applications. Therefore, a better knowledge of the mechanism of transfection mediated by non-viral vectors will allow the development of more efficient non-viral vectors for gene therapy applications
Structural and functional studies of the Escherichia coli SecA by tryptophan fluorescence spectroscopy
No full textEiwitten die in een biologische cel worden aangemaakt, maar buiten de cel hun werk moeten doen, verlaten de cel via poriën in het celmembraan. Deze poriën zijn actieve transportkanalen, samengesteld uit verschillende eiwitten. Paolo Natale deed onderzoek naar de wijze waarop eiwitten door dit transportkanaal worden geleid
An empirical test of Birkett's competency model for management accountants: A confirmative study in the Netherlands
No full textBisthioxanthylidene biscrown ethers as potential stereodivergent chiral ligands
No full textThe concept of bisthioxanthylidene biscrown ethers as potential stereodivergent chiral ligands in asymmetric synthesis is introduced. Substituted bisthioxanthylidenes may be chiral and can exist as stable enantiomers due to their folded structure. As a result, both a right-handed helix (P) and left-handed helix (M) are present in this type of molecule. This offers the unique possibility to construct two crown ether moieties, attached to the same molecule, of which one exhibits (P)-helicity and the other (M)-helicity. When the crown ether moieties differ in size they can be complexed selectively with a base containing a cation of appropriate diameter. In this manner the (P)-helix and the (M)-helix can be activated selectively to serve as a chiral environment for base catalyzed asymmetric synthesis. Thus, we envisioned the new concept of a single chiral ligand to separately synthesize two enantiomers of a chiral product just by varying the added base. For this purpose, four new bisthioxanthylidene monocrown ethers and two new bisthioxanthylidene biscrown ethers were synthesized. Two biscrowns and two monocrowns were separated into their respective enantiomers (HPLC) and optical data (UV and CD) were collected to ensure stability of enantiomers at ambient temperatures. Ion complexation of one mono- and two biscrown ethers with potassium and sodium cations was investigated.</p
Highly enantioselective Cu-catalysed allylic substitutions with Grignard reagents
No full textA catalyst system able to perform highly enantioselective Cu-catalysed allylic alkylations with Grignard reagents is described.</p
