Interactions of the Antiviral Quinoxaline Derivative 9-OH-B220 {2,3-dimethyl-6-(dimethylaminoethyl)-9-hydroxy-6H-indolo-[2,3-b] quinoxaline} with Duplex and Triplex forms of Synthetic DNA and RNA

The binding of an antiviral quinoxaline derivative, 2,3-dimethyl-6-(dimethylaminoethyl)-9 -hydroxy-6H-indolo-[2,3-b]quinoxaline (9-OH-B220), to synthetic double and triple helical DNA (poly(dA).poly(dT) and poly(dA.)2poly(dT)) and RNA (poly(rA).poly(rU) and poly(rA) .2poly(rU)) has been characterized using flow linear dichroism (LD), circular dichroism (CD), fluorescence spectroscopy, and thermal denaturation. When either of the DNA structures or the RNA duplex serve as host polymers a strongly negative LD is displayed, consistent with intercalation of the chromophoric ring system between the base-pairs/triplets of the nucleic acid structures. Evidence for this geometry also includes weak induced CD signals and strong increments of the fluorescence emission intensities upon binding of the drug to each of these polymer structures. Ln agreement with intercalative binding, 9-OH-B220 is found to effectively enhance the thermal stability of both the double and triple helical states of DNA as well as the RNA duplex. Ln the case of poly(dA).2poly(dT), the drug provides an unusually large stabilization of its triple helical state; upon binding of 9-OH-B220 the tripler-to-duplex equilibrium is shifted towards higher temperature by 52.5 deg. C in a 10 mM sodium cacodylate buffer (pH 7.0) containing 100 mM NaCl and 1 mM EDTA. When triplex RNA serves as host structure, LD indicates that the average orientation angle between the drug chromophore plane and the helix axis of the triple helical RNA is only about 60 to 65 degrees. Moreover, the thermal stabilizing capability, as well as the fluorescence increment, CD inducing power and perturbations of the absorption envelope, of 9-OH-B220 in complex with the RNA tripler are all less pronounced than those observed for the complexes with DNA and duplex RNA. These features indicate binding of 9-OH-B220 in the wide and shallow minor groove of poly(rA).2poly(rU). Based on the present results, some implications for the applications of this low-toxic, antiviral and easily administered drug in an antigene strategy, as well as its potential use as an antiretroviral agent, are discusse

THE INTERACTION OF ELLIPTICINE DERIVATIVES WITH NUCLEIC-ACIDS STUDIED BY OPTICAL AND H-1-NMR SPECTROSCOPY - EFFECT OF SIZE OF THE HETEROCYCLIC RING

The DNA interaction of derivatives of ellipticine with heterocyclic ring systems with three, four, or five rings and a dimethylaminoethyl side chain was studied. Optical spectroscopy of drug complexes with calf thymus DNA, poly [(dA-dT).(dA-dT)], or poly [(dG-dC).(dG-dC)] showed a 10 nm bathochromic shift of the light absorption bands of the pentacyclic and tetracyclic compounds upon binding to the nucleic acids, which indicates binding by intercalation. For the tricyclic compound a smaller shift of 1-3 nm was observed upon binding to the nucleic acids. Flow linear dichroism studies show that the geometry of all complexes is consistent with intercalation of the ring system, except for the DNA and poly [(dG-dC).(dG-dC)] complexes of the tricyclic compound, where the average angle between the drug molecular plane and the DNA helix axis was found to be 65 degrees. One-dimensional H-1-nmr spectroscopy was used to study complexes between d(CGCGATCGCG)(2) and the tricyclic and pentacyclic compounds. The results on the pentacyclic compound show nonselective broadening due to intermediate chemical exchange of most oligonucleotide resonances upon drug binding. The imino proton resonances are in slow chemical exchange, and new resonances with upheld shifts approaching 1 ppm appear upon drug binding, which supports intercalative binding of the pentacyclic compound. The results on the tricyclic compound show more rapid binding kinetics and very selective broadening of resonances. The data suggest that the tricyclic compound is in an equilibrium between intercalation and minor groove binding, with a preference to bind close to the AT base pairs with the side chain residing in the minor groove. (C) 1994 John Wiley and Sons, Inc

What may characterise teaching in preschool? : The written descriptions of Swedish preschool teachers and managers in 2016

This paper addresses national concern about teaching in preschool, building on the challenges, opportunities, and requirements facing today’s preschools due to the higher expected level of preschool assignments. The aim is to build knowledge of how preschool teachers and managers from ten Swedish municipalities characterise preschool teaching. The material was generated in a 2016 survey completed by 243 respondents (91% response rate). A didactics-oriented textual analysis referred to Kansanen’s (1993) three-level schema comprising the action, theoretical, and meta-theoretical levels and the results identify eight distinctive traces ranging from the rejection to the recognition of preschool teaching. Recognition traces emphasise wide-ranging, diffuse, and child-centred teaching. The results indicate that traces of the action level are more prominent and ‘multivocal’ than are traces of the theoretical and meta-theoretical levels. Overall, the combined analytical results support the concept of ‘diffuse multivocal teaching’

Att skapa läroplan för de yngsta barnen i förskolan. Barns perspektiv och nuets didaktik

This thesis takes as one point of departure the concept of the expanded curriculum where curricula encompass both the formal steering documents, as well as that which goes on within the framework of preschool education and through the actors in preschools. The overarching purpose is therefore to generate knowledge about what conditions for learning the work of teachers make possible when curricula are created in preschool settings for children aged between 1 and 3. The purpose is also to contribute with knowledge about what these created curricula would mean for children’s agency, and the importance they can have for children’s opportunities for learning and development. The three empirical studies consist of digitally recorded interviews with teachers and video observations with a focus on teachers’ communication with children in preschool. The discussion in the overarching text is constructed around three aspects that emerge in the overall results of the studies. First, the studies reveal how teachers’ work can be likened to a limiting curriculum which, on the one hand, is entirely child-centered, with the children as seen actors, but, on the other, can be interpreted as entirely teacher-centered. Secondly, there is the discussion about the affirmative curriculum, where children are presented as affirmed actors. In other words, content becomes those things that children are interested in, and their modes of expression are seen, affirmed and often repeated. Finally there is the discussion about the possibilities and dilemmas related to an expanding curriculum where children are regarded and treated as real actors in the sense that their intentions and expressions are taken seriously as relevant challenges. The current curriculum text for Swedish preschool can, in this sense, be seen as an obstacle in that its formulations are extremely broad-based, as discussed related to the results of this thesis