Crystal Engineering of an Anti-HIV Drug Based on the Recognition of Assembling Molecular Frameworks

A rational strategy was employed for design of an orthorhombic structure of lamivudine with maleic acid. On the basis of the lamivudine saccharinate structure reported in the literature, maleic acid was chosen to synthesize a salt with the anti-HIV drug because of the structural similarities between the salt formers. Maleic acid has an acid-ionization constant of the anti first proton and an arrangement of their hydrogen bonding functionalities similar to those of saccharin. Likewise, there is a saccharin-like conformational rigidity in maleic acid because of the hydrogen-bonded ring formation and the Z-configuration around the C=C double bond. As was conceivably predicted, lamivudine maleate assembles into a structure whose intermolecular architecture is related to that of saccharinate salt of the drug. Therefore, a molecular framework responsible for crystal assembly into a lamivudine saccharinate-like structure could be recognized in the salt formers. Furthermore, structural correlations and structure-solubility relationships were established for lamivudine maleate and saccharinate. Although there is a same molecular framework in maleic acid and saccharin, these salt formers are Structurally different in some aspects. When compared to saccharin, neither out-of-plane SO(2) oxygens nor a benzene group occur in maleic acid. Both features could be related to higher solubility of lamivudine maleate. Here, we also anticipate that multicomponent molecular crystals of lamivudine with other salt formers possessing the molecular framework responsible for crystal assembly can be engineered successfully.

Superoxide Dismutase 1-mediated Production of Ethanol- and DNA-derived Radicals in Yeasts Challenged with Hydrogen Peroxide MOLECULAR INSIGHTS INTO THE GENOME INSTABILITY OF PEROXIREDOXIN-NULL STRAINS

Peroxiredoxins are receiving increasing attention as defenders against oxidative damage and sensors of hydrogen peroxide-mediated signaling events. In the yeast Saccharomyces cerevisiae, deletion of one or more isoforms of the peroxiredoxins is not lethal but compromises genome stability by mechanisms that remain under scrutiny. Here, we show that cytosolic peroxiredoxin-null cells (tsa1 Delta tsa2 Delta) are more resistant to hydrogen peroxide than wildtype (WT) cells and consume it faster under fermentative conditions. Also, tsa1 Delta tsa2 Delta cells produced higher yields of the 1-hydroxyethyl radical from oxidation of the glucose metabolite ethanol, as proved by spin-trapping experiments. A major role for Fenton chemistry in radical formation was excluded by comparing WT and tsa1 Delta tsa2 Delta cells with respect to their levels of total and chelatable metal ions and of radical produced in the presence of chelators. The main route for 1-hydroxyethyl radical formation was ascribed to the peroxidase activity of Cu, Zn-superoxide dismutase (Sod1), whose expression and activity increased similar to 5- and 2-fold, respectively, in tsa1 Delta tsa2 Delta compared with WT cells. Accordingly, overexpression of human Sod1 in WT yeasts led to increased 1-hydroxyethyl radical production. Relevantly, tsa1 Delta tsa2 Delta cells challenged with hydrogen peroxide contained higher levels of DNA-derived radicals and adducts as monitored by immuno-spin trapping and incorporation of (14)C from glucose into DNA, respectively. The results indicate that part of hydrogen peroxide consumption by tsa1 Delta tsa2 Delta cells is mediated by induced Sod1, which oxidizes ethanol to the 1-hydroxyethyl radical, which, in turn, leads to increased DNA damage. Overall, our studies provide a pathway to account for the hypermutability of peroxiredoxin-null strains.

1,4-Dioxane enhances properties and biocompatibility of polyanionic collagen for tissue engineering applications

Polyanionic collagen obtained from bovine pericardial tissue submitted to alkaline hydrolysis is an acellular matrix with strong potential in tissue engineering. However, increasing the carboxyl content reduces fibril formation and thermal stability compared to the native tissues. In the present work, we propose a chemical protocol based on the association of alkaline hydrolysis with 1,4-dioxane treatment to either attenuate or revert the drastic structural modifications promoted by alkaline treatments. For the characterization of the polyanionic membranes treated with 1,4-dioxane, we found that (1) scanning electron microscopy (SEM) shows a stronger reorientation and aggregation of collagen microfibrils; (2) histological evaluation reveals recovering of the alignment of collagen fibers and reassociation with elastic fibers; (3) differential scanning calorimetry (DSC) shows an increase in thermal stability; and (4) in biocompatibility assays there is a normal attachment, morphology and proliferation associated with high survival of the mouse fibroblast cell line NIH3T3 in reconstituted membranes, which behave as native membranes. Our conclusions reinforce the ability of 1,4-dioxane to enhance the properties of negatively charged polyanionic collagen associated with its potential use as biomaterials for grafting, cationic drug- or cell-delivery systems and for the coating of cardiovascular devices.

European Solar Engineering School ESES : Past and Future

The European Solar Engineering School ESES is a one-year masters program that started in 1999 at the Solar Energy Research Center SERC, Dalarna University College. It has been growing in popularity over the years, with over 20 students in the current year. Approximately half the students come from Europe, the rest coming from all over the globe. This paper described the contents and experiences from seven years of running the programme and the plans for adapting the programme to the Bologna process. The majority of the students from ESES have found work in the solar industry, energy industry or taken up PhD positions. An alumni group has been started that actively gives support to past, present and potential future students.

Sustainability and research integrated in engineering courses at Dalarna University, Sweden

Högskolepedagogik, högskolepedagogisk utbildning, BHU

Constructive alignment in Computer Engineering and Informatics departments at Dalarna University : An empirical investigation

Background: Constructive alignment (CA) is a pedagogical approach that emphasizes the alignment between the intended learning outcomes (ILOs), teaching and learning activities (TLAs) and assessment tasks (ATs) as well as creation of a teaching/learning environment where students will be able to actively create their knowledge. Objectives: This paper aims at investigating the extent of constructively-aligned courses in Computer Engineering and Informatics department at Dalarna University, Sweden. This study is based on empirical observations of teacher’s perceptions of implementation of CA in their courses. Methods: Ten teachers (5 from each department) were asked to fill a paper-based questionnaire, which included a number of questions related to issues of implementing CA in courses. Results: Responses to the items of the questionnaire were mixed. Teachers clearly state the ILOs in their courses and try to align the TLAs and ATs to the ILOs. Computer Engineering teachers do not explicitly communicate the ILOs to the students as compared to Informatics teachers. In addition, Computer Engineering teachers stated that their students are less active in learning activities as compared to Informatics teachers. When asked about their subjective ratings of teaching methods all teachers stated that their current teaching is teacher-centered but they try to shift the focus of activity from them to the students. Conclusions: From teachers’ perspectives, the courses are partially constructively-aligned. Their courses are “aligned”, i.e. ILOs, TLAs and ATs are aligned to each other but they are not “constructive” since, according to them, there was a low student engagement in learning activities, especially in Computer Engineering department.

Initiation into engineering : stability and change in gender orders

This article examines processes of doing gender during the initiation of students into engineering programs at university level in Sweden. The article draws on interviews with students, focusing on their understandings of gender. The aim is to explore difficulties with and challenges to traditional gender roles in an academic male dominated arena, by using theories of doing and undoing gender. The empirical material reveals the initiation period or ‘reception’ as a phenomenon both reinforcing and challenging traditional orders. The attempts to challenge norms meet resistance, revealing two paradoxes and one dilemma. In the first paradox the formal purpose of the reception (inclusion) is partly at odds with its informal consequence (exclusion of deviations). The second paradox concerns the contradictory effects of the reception. Even though the reception ensures participation of women, it reinforces existing hierarchies including gender inequality. This results in a dilemma, since in order to protect individual safety, there is a taboo on harassing women which then reproduces stable gender stereotypes. So while harassment taints the respect senior students must earn during the reception, the fact that female students exist in the engineering field challenges the established order and opens the way for change.

Genome-wide association mapping in a wild avian population identifies a link between genetic and phenotypic variation in a life-history trait

Understanding the genetic basis of traits involved in adaptation is a major challenge in evolutionary biology but remains poorly understood. Here, we use genome-wide association mapping using a custom 50 k single nucleotide polymorphism (SNP) array in a natural population of collared flycatchers to examine the genetic basis of clutch size, an important life-history trait in many animal species. We found evidence for an association on chromosome 18 where one SNP significant at the genome-wide level explained 3.9% of the phenotypic variance. We also detected two suggestive quantitative trait loci (QTLs) on chromosomes 9 and 26. Fitness differences among genotypes were generally weak and not significant, although there was some indication of a sex-by-genotype interaction for lifetime reproductive success at the suggestive QTL on chromosome 26. This implies that sexual antagonism may play a role in maintaining genetic variation at this QTL. Our findings provide candidate regions for a classic avian life-history trait that will be useful for future studies examining the molecular and cellular function of, as well as evolutionary mechanisms operating at, these loci.