Search

The glucagon-like peptide 1 (GLP-1) analog, liraglutide, is a GLP-1 agonist and is used in the treatment of type-2 diabetes mellitus and obesity. From a pharmaceutical perspective, it is important to know the oligomerization state of liraglutide with respect to stability. Compared to GLP-1, liraglutide has an added fatty acid (FA) moiety that causes oligomerization of liraglutide as suggested by small-angle x-ray scattering (SAXS) and multiangle static light scattering (MALS) results. SAXS data suggested a global shape of a hollow elliptical cylinder of size hexa-, hepta-, or octamer, whereas MALS data indicate a hexamer. To elaborate further on the stability of these oligomers and the role of the FA chains, a series of molecular-dynamics simulations were carried out on 11 different hexa-, hepta-, and octameric systems. Our results indicate that interactions of the fatty acid chains contribute noticeably to the stabilization. The simulation results indicate that the heptamer with paired FA chains is the most stable oligomer when compared to the 10 other investigated structures. Theoretical SAXS curves extracted from the simulations qualitatively agree with the experimentally determined SAXS curves supporting the view that liraglutide forms heptamers in solution. In agreement with the SAXS data, the heptamer forms a water-filled oligomer of elliptical cylindrical shape.

We have performed a series of thermodynamic measurements and molecular dynamics (MD) simulations to study the interactions between the neurotransmitters (NTs) 5-hydroxytryptamine (5-HT), g-aminobutyrate (GABA), glycine (GLY), acetylcholine (ACH) and glutamate (GLU) as well as the amidated / acetylated g-aminobutyrate (GABAneu) with a dipalmitoylphosphatidylcholine (DPPC) bilayer. This study was motivated by recent research results that suggested that neural transmission may also be affected by nonspecific interactions of NTs with the lipid matrix of the synaptic membrane. Our results revealed that dependent on the nature of NTs, some of the NTs penetrate into the bilayer. We found that membrane affinity can be ranked with increasing affinity as follows: ACH ~ GLU << GABA < GLY << GABAneu << 5-HT. The latter three penetrated the bilayer at most with the deepest location being close to the glycerol backbone of the phospholipids. It is surprising that hydrophilic solutes can deeply penetrate into the membrane pointing to the fact that membrane affinity is governed by specific interactions. Our MD simulations identified the salt-bridge between the primary amine of NTs and the lipid phosphate group as the most important interaction by which the NTs are anchored to the membrane. These distinctive interactions could be related to nonspecific effects of these neurotransmitters and could point to a bilayer-mediated modulation of nerve transmission. However, due to the strong variability in affinity observed for the different NTs, this attraction is not an inherent property of all neurotransmitters.

Mitochondria are crucial to iron metabolism, being the unique site for heme synthesis and the major site for iron-sulfur (Fe-S) cluster biosynthesis. Iron is transported into the mitochondrion by an iron metal transporter, mitoferrin, in the inner membrane of mitochondria. By studying different dmfrn Drosophila mutants we have previously showed that dmfrn and mitochondrial iron metabolism have an important role during spermatogenesis and that a functional dmfrn is essential for male fertility (Metzendorf & Lind, 2010). During the spermatogenesis study, we characterized two fly strains with deletions in the dmfrn gene, which is located on the right arm of chromosome three. In the strain with the small deletion dmfrnDf13, which we recovered during P-element mobilization, a third of the 5´ untranslated region is deleted. In the strain Df(3R)ED6277, the genes dmfrn and CG5514 are deleted and half of the 5´ untranslated regions of genes Mes-4 and Gp93 are removed. We found that deletion of dmfrn, (homozygous dmfrnDf13, transheterozygous dmfrnDf13/Df(3R)ED6277 or homozygous Df(3R)ED6277) causes lethality at larval stage. In the current study we analyzed the developmental phenotype in further detail. As fertility of the hypomorph dmfrn P element mutant strains is depended on the level of dietary iron (Metzendorf & Lind, 2010), we were interested if the deletion mutants might show a similar dependence. Using a third chromosome balancer with markers, Tb (Tubby will result in shorter larvae and pupae) and Sb (stubble: bristles short and stubby) that allows distinguishing between heterozygous and transheterozygous flies at the larval, pupal and adult stage makes it possible to quantify the genotypes. We found that transheterozygous (dmfrnDf13/Df(3R)ED6277) flies develop to third instar larvae and very seldom start puparation (<0.25%) when the flies was fed with low iron food. On normal food, transheterozygous flies develop to the pupal stage (~17%), but very few fli

AuthorCount:2

In this thesis, density functional theory has been employed to study the reactionmechanisms of two enzymes with possible applications in asymmetric biocatalysis.To reproduce and rationalize the stereoselectivity of the enzymes, quite large cluster models that account for the chiral environment of the active site have been used. In the first study, the enantioselectivity of the wild-type limonene epoxidehydrolase and two groups of mutants thereof, that show either (R,R)- or (S,S)-selectivity, were investigated. Using the cluster approach, the enantioselectivity for each variant of the enzyme was calculated and the results are in good agreement with the experimental data. It was found that the enantioselectivity of the enzyme variants is controlled by the steric hindrance introduced or relieved bythe different mutations. The second study concerns the reaction mechanism and stereoselectivity of arylmalonate decarboxylase. The calculations support the proposed two-step mechanism, in which decarboxylation and protonation of the substrate occur separately. The stereoselectivity of the enzyme is governed by repulsive steric interactions between the substrate and the residues that deffine a large and a small cavity in the active site. Depending on the size of the substrate, the selectivity was found to be determined already at the binding of the substrate or in the subsequent transition state. The results presented in this thesis demonstrate that the quantum chemical cluster approach for modeling enzymes is indeed a very valuable tool in the study of asymmetric biocatalysis.

Aim: To investigate conversations between nurses and parents in Swedish child health services and to assess to what extent attention is directed towards dietary and physical activity behaviours in children. Methods: Twenty-three nurses audio-recorded one session each. Recordings were assessed and topics were classified according to predetermined categories. Results: The three most frequent topics of conversation concerned physical examinations of the child (30% of session time), talking to the child to establish or maintain contact and interest (15%), and development of language skills (12%). Dietary habits came on fourth place (10%), and physical activity ranked 14 (4%). Conclusion: Attention to dietary and physical activity behaviours in children is infrequent in Swedish child health services. Concern is raised about the efficacy of prevention efforts against childhood obesity., Funding Agency:Swedish Council for Working Life and Social Research 2006-0226 2011-0413 Swedish Diabetes Association TMA2006-004 Uppsala County Council

The commercial methods and transactional processes of the art market contravene in almost every way the free market principles and investment assumptions and patterns core to modern global finance. What Noah Horowitz calls the art market’s "anti-speculative vehemence" is intimately allied to its protagonist’s amorous-erotic investment in art, widely flaunted in the highly visible acquisition of blue-chip art by capitalist elites as much as in the cloying discourses in public and private art sectors supporting and relying upon such expenditure. The centrality of this amorous ethos to the concentration of social and capital power in art relies upon and maintains the belief that while art is indeed traded on a market it is rather that market’s obstruction of liberal free-market principles and practices that accords with an involvement in art itself. Simultaneously, the domination of capital power in art means that art’s audiences are now obliged to share in the capriciousness of the subjective love of art allied to the corporatism of capital power rather than a previously assumed statist 'care' for public culture, providing in the process an ersatz-public legitimization for such power. This paper seeks to remove the support for the decontamination of capitalized power through art’s amorous ethos. Since art-prices are explicitly financially generated without reference to production or consumption, they make manifest the condition of all price-setting—or what could be called capital’s procedural and operational “financiality”, the term designating finance as the primary condition for, rather than consequence of, capitalization and price-setting. As such, the art market embodies the truth of finance, and it does so precisely in its failure or limitations of art as a kind of free-market investment. It is not then that art pricing is a puzzle compared to other, productive or consuming, sectors of the economy, but that the art market dispels their obscuring of capitalization

Insects protect themselves against microbial infection by an efficient innate immune system that is activated by recognition of invariant microbial surface molecules. In the fruit fly Drosophila melanogaster the presence of bacteria is associated with expression of antimicrobial peptides in host immune-competent tissues. Host receptors detect infection and relay the signal to mount the appropriate immune response. In Drosophila hemocyte-like l(2)mbn cells pre-infection treatment with Pefabloc, a commonly used serine protease inhibitor, induced two major effects: it blocked expression of the antibacterial peptide Diptericin in response to live Gram-negative bacteria and bacterial surface molecules (crude lipopolysaccharide contaminated by peptidoglycans) and it induced morphological changes.

Background: Nurses´daily has to face death and dying in their work with patients in a palliative state. This means both emotionell and workrelated challenges. However nurses in this context are not experiencing more stress then others. Aim: The aim is to describe nurses´experiences of caring for patients in a palliative state. Method: A litterature review based on ten qualitative articles published between 2006- 2012. To collect data we used the databases Cinahl, PubMed, Nursing Allied Health Source and Medline. We worked with Fribergs (2006) model ”Contribute to evidensbased care with a base in analyses of qualitative science” in the analysis. Result: Four main themes were identified; The meaning of the nurses´ spirituality in the care, Why the nurse choose to work in this field, To be certain in the professional role and The meaning of the caring relationship. In these are nine subthemes included; To evole through insights, Making a difference, To feel satisfaction in their work, The importance of experience, The importance of colleagues, The importance of competence, Positive effects related to the relationship, Negative effects related to the relationship samt Finding a balance between work and private life. Discussion: The results were discussed using the model KASAM by A. Antonovsky . The results shows that nurses´motivation in their work comes from their sense of meaningfulness which impacts the care that is given by him/her. In addition, we looked at the results from the four cornerstones in palliative care. Keywords: Nurse perspective, palliative care, death, dying, experience, meaning.

"Over the past twenty years, an abundance of art forms have emerged that use aesthetics to affect social dynamics. These works are often produced by collectives or come out of a community context; they emphasize participation, dialogue, and action, and appear in situations ranging from theater to activism to urban planning to visual art to health care. Engaged with the texture of living, these art works often blur the line between art and life. This book offers the first global portrait of a complex and exciting mode of cultural production — one that has virtually redefined contemporary art practice. Living as Form grew out of a major exhibition at Creative Time in New York City. Like the exhibition, the book is a landmark survey of more than 100 projects selected by a thirty-person curatorial advisory team; each project is documented by a selection of color images. The artists include the Danish collective Superflex, who empower communities to challenge corporate interest; Turner Prize nominee Jeremy Deller, creator of socially and politically charged performance works; Women on Waves, who provide abortion services and information to women in regions where the procedure is illegal; and Santiágo Cirugeda, an architect who builds temporary structures to solve housing problems" -- p. [4] of cover.

Background: Mammals and Drosophila melanogaster share some striking similarities in spermatogenesis. Mitochondria in spermatids undergo dramatic morphological changes and syncytial spermatids are stripped from their cytoplasm and then individually wrapped by single membranes in an individualization process. In mammalian and fruit fly testis, components of the mitochondrial iron metabolism are expressed, but so far their function during spermatogenesis is unknown. Here we investigate the role of Drosophila mitoferrin (dmfrn), which is a mitochondrial carrier protein with an established role in the mitochondrial iron metabolism, during spermatogenesis. Results: We found that P-element insertions into the 5'-untranslated region of the dmfrn gene cause recessive male sterility, which was rescued by a fluorescently tagged transgenic dmfrn genomic construct (dmfrn(venus)). Testes of mutant homozygous dmfrn(SH115) flies were either small with unorganized content or contained some partially elongated spermatids, or testes were of normal size but lacked mature sperm. Testis squashes indicated that spermatid elongation was defective and electron micrographs showed mitochondrial defects in elongated spermatids and indicated failed individualization. Using a LacZ reporter and the dmfrn(venus) transgene, we found that dmfrn expression in testes was highest in spermatids, coinciding with the stages that showed defects in the mutants. Dmfrn-venus protein accumulated in mitochondrial derivatives of spermatids, where it remained until most of it was stripped off during individualization and disposed of in waste bags. Male sterility in flies with the hypomorph alleles dmfrn(BG00456) and dmfrn(EY01302) over the deletion Df(3R)ED6277 was increased by dietary iron chelation and suppressed by iron supplementation of the food, while male sterility of dmfrn(SH115)/Df(3R)ED6277 flies was not affected by food iron levels. Conclusions: In this work, we show that mutations in the Drosophila mi, Uppdaterad från Manuskript till Artikel 20101208

Studien har syftat till att undersöka samband mellan samsjuklig psykologisk problematik och katastroftänkande hos ungdomar utifrån ett transdiagnostiskt perspektiv. Katastroftänkandets roll för förändring av social ångest och depressiva symtom undersöktes utifrån en studie av internetbaserad KBT-behandling mot social fobi (N=18). Resultatet indikerar att ungdomar med hög initial nivå av katastroftänkande har större reduktion av depressiva symtom än ungdomar med låg nivå av katastroftänkande. Detta talar för att hänsyn bör tas till grad av katastroftänkande vid utformning av behandling för personer med social fobi, särskilt vid samsjuklighet med depression. Kopplingen mellan katastroftänkande och samsjuklighet undersöktes utifrån en tvärsnittsstudie av gymnasieungdomar (N=713). Resultatet visar på en koppling mellan katastroftänkande och social rädsla, sömnproblematik och nedstämdhet., This study was aimed at examining the relationship between co-existing psychological problems and catastrophizing in adolescents from a transdiagnostic perspective. The role of catastrophizing for the change of social anxiety and depression was analyzed in an internet based CBT-treatment for social phobia (N=18). The results indicate that adolescents with high initial level of catastrophizing have a larger reduction of depression than adolescents with low initial level of catastrophizing. This suggests that catastrophizing should be considered when specifying treatment for social phobia, especially if it co-occurs with depression. The relationship between catastrophizing and comorbidity was analyzed in a cross-sectional study of adolescents (N=713). The result suggests that catastrophizing is associated with the level of social fear, sleep problems and depression.

Mrs3p and Mrs4p (Mrs3/4p) are yeast mitochondrial iron carrier proteins that play important roles in ISC (iron-sulphur cluster) and haem biosynthesis. At low iron conditions, mitochondrial and cytoplasmic ISC protein maturation is correlated with MRS3/4 expression. Zebrafish mitoferrin1 (mfrn1), one of two MRS3/4 orthologues, is essential for erythropoiesis, but little is known about the ubiquitously expressed paralogue mfrn2. In the present study we identified a single mitoferrin gene (dmfrn) in the genome of Drosophila melanogaster, which is probably an orthologue of mfrn2. Overexpression of dmfrn in the Drosophila l(2)mbn cell line (mbn-dmfrn) resulted in decreased binding between IRP-1A (iron regulatory protein 1A) and stem-loop RNA structures referred to as IREs (iron responsive elements). mbn-dmfrn cell lines also had increased cytoplasmic aconitase activity and slightly decreased iron content. In contrast, iron loading results in decreased IRP-1A-IRE binding, but increased cellular iron content, in experimental mbn-dmfrn and control cell lines. Iron loading also increases cytoplasmic aconitase activity in all cell lines, but with slightly higher activity observed in mbn-dmfrn cells. From this we concluded that dmfrn overexpression stimulates cytoplasmic ISC protein maturation, as has been reported for MRS3/4 overexpression. Compared with control cell lines, mbn-dmfrn cells had higher Fer1HCH (ferritin 1 heavy chain homologue) transcript and protein levels. RNA interference of the putative Drosophila orthologue of human ABCB7, a mitochondrial transporter involved in cytoplasmic ISC protein maturation, restored Fer1HCH transcript levels of iron-treated mbn-dmfrn cells to those of control cells grown in normal medium. These results suggest that dmfrn overexpression in l(2)mbn cells causes an 'overestimation' of the cellular iron content, and that regulation of Fer1HCH transcript abundance probably depends on cytoplasmic ISC protein maturation.

The mitochondrial inner membrane is the central energy-converting membrane of eukaryotic cells. the electrochemical proton gradient generated by the respiratory chain drives the ATP synthase. to maintain this proton-motive force, the inner membrane forms a tight barrier and strictly controls the translocation of ions(1). However, the major preprotein transport machinery of the inner membrane, termed the presequence translocase, translocates polypeptide chains into or across the membrane(2-9). Different views exist of the molecular mechanism of the translocase, in particular of the coupling with the import motor of the matrix(8,10,11). Wehave reconstituted preprotein transport into the mitochondrial inner membrane by incorporating the purified presequence translocase into cardiolipin-containing liposomes. We show that the motor-free form of the presequence translocase integrates preproteins into the membrane. the reconstituted presequence translocase responds to targeting peptides and mediates voltage-driven preprotein translocation, lateral release and insertion into the lipid phase. thus, the minimal system for preprotein integration into the mitochondrial inner membrane is the presequence translocase, a cardiolipin-rich membrane and a membrane potential.

Syftet är att beskriva och analysera utformningen och tillämpningen av Balanced Scorecard i en sjukvårdsverksamhet samt studera huruvida modellen används som ett mätsystem eller ett managementsystem. Metoden som ligger till grund för denna uppsats är kvalitativ i form av en djupare fallstudie av en sjukvårdsverksamhet. Vi har utgått från såväl sekundärdata som primärdata för att erhålla relevant information till uppsatsen. Primärdata har samlats in via personliga intervjuer. Det teoretiska kapitlet innehåller modeller och begrepp som behandlar budget, BSC, ekonomistyrning i offentlig verksamhet och i sjukvården. Det empiriska kapitlet behandlar en fallstudie av Hjärt- och Lungdivisionen på Universitetssjukhuset i Lund, där divisionens ekonomistyrning i form av budget och BSC beskrivs. En jämförelse mellan teori om BSC och Hjärt- och Lungdivisionens BSC har visat på en hel del likheter, men även vissa skillnader. Fallföretagets BSC har en struktur som liknar den som beskrivs av Kaplan och Norton, men styrkortet har anpassats till organisationens specifika miljö. Avsaknaden av vissa faktorer som t.ex. orsak-verkan samband och balans i styrkortet gör att det är svårt att klassificera Hjärt- och Lungdivisionens BSC som ett fulländat managementsystem.

The cDNA cloning of the 76-kDa protein, an immune protein from crayfishhaemocytes, shows that it is similar to a family of haem-containing peroxidases.In addition to its cell adhesion activity it has also peroxidase activity, and theprotein was named peroxinectin. The cell adhesion is probably mediated by aKGD-motif present in peroxinectin. In mammals, the iron-regulatory proteins (IRP) can bind the iron-responsive element (IRE), present in the mRNAs of some iron proteins andthereby regulate their expression. IRPs are also present in the invertebrates,Drosophila melanogaster, and Pacifastacus leniusculus. Two DrosophilaIRP1s, IRP1A and IRP1B, were cloned. Recombinant IRP1A binds specifically toIREs and both IRP1A and IRP1B have aconitase activity. The Drosophilamitochondrial aconitase (mAc) was cloned and shows similarity to the IRPs.Interestingly, the Drosophila mAc mRNA lacks the IRE, in contrast tomammalian mAc transcripts, which have IREs. This supports the idea thatDrosophila has another IRP regulated step in the citric acid cycle. Several transcripts encoding the same ferritin subunit in D.melanogaster were isolated. These transcripts are generated by alternativesplicing and differential poly-adenylation. The expressions of these aredevelopmentally regulated, and are modulated in response to the iron level. AnIRE is present within the alternatively spliced intron. Furthermore, the transcriptencoding crayfish ferritin has an atypical IRE. Both the Drosophila and crayfish ferritin IREs bind specifically to IRPs. Translocation of iron and other metal-ions through the bilipidmembrane is depending on transport systems, and in Drosophila three members of the ZIP family of metal-ion transporters were identified and their expression was studied.

Joan Flasch Artists' Book Collection