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Sökning: WFRF:(Westerlund Anna 1978 )

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1.
  • Lindberg, David, 1986-, et al. (författare)
  • Binding of Thioflavin-T to Amyloid Fibrils Leads to Fluorescence Self-Quenching and Fibril Compaction
  • 2017
  • Ingår i: Biochemistry. - 0006-2960. ; 56:16, s. 2170-2174
  • Tidskriftsartikel (refereegranskat)abstract
    • Thioflavin-T binds to and detects amyloid fibrils via fluorescence enhancement. Using a combination of linear dichroism and fluorescence spectroscopies, we report that the relation between the emission intensity and binding of thioflavin-T to insulin fibrils is nonlinear and discuss this in relation to its use in kinetic assays. We demonstrate, from fluorescence lifetime recordings, that the nonlinearity is due to thioflavin-T being sensitive to self-quenching. In addition, thioflavin-T can induce fibril compaction but not alter fibril structure. Our work underscores the photophysical complexity of thioflavin-T and the necessity of calibrating the linear range of its emission response for quantitative in vitro studies.
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2.
  • Nordell, Pär, 1978-, et al. (författare)
  • DNA Polymorphism as an Origin of Adenine-Thymine Tract Length-Dependent Threading Intercalation Rate
  • 2008
  • Ingår i: Journal of the American Chemical Society. - 0002-7863. ; 130:44, s. 14651-14658
  • Tidskriftsartikel (refereegranskat)abstract
    • Binuclear ruthenium complexes that bind DNA by threading intercalation have recently been found to exhibit an exceptional kinetic selectivity for long polymeric adenine-thymine (AT) DNA. A series of oligonucleotide hairpin duplexes containing a central tract of 6-44 alternating AT base pairs have here been used to investigate the nature of the recognition mechanism. We find that, above a threshold AT tract length corresponding to one helix turn of B-DNA, a dramatic increase in threading intercalation rate occurs. In contrast, such length dependence is not observed for rates of unthreading. Intercalation by any mechanism that depends on the open end of the hairpin was found not to be important in the series of oligonucleotides used, as verified by including in the study a hairpin duplex cyclized by a copper-catalyzed "click" reaction. Our observations are interpreted in terms of a conformational pre-equilibrium, determined by the length of the AT tract. We finally find that mismatches or loops in the oligonucleotide facilitate the threading process, of interest for the development of mismatch-recognizing probes. © 2008 American Chemical Society.
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3.
  • Nordell, Pär, 1978-, et al. (författare)
  • Finding at-DNA--kinetic recognition of long adenine-thymine stretches by metal-ligand complexes.
  • 2008
  • Ingår i: Nucleic acids symposium series (2004). - 1746-8272. ; :52, s. 131-132
  • Tidskriftsartikel (refereegranskat)abstract
    • High selectivity for long AT sequences can be attained by kinetically controlled DNA threading intercalation by binuclear ruthenium(II) complexes. The rate of intercalation is strongly correlated to the number of consecutive AT basepairs, being up to 2500 times faster with an AT polymer compared to mixed-sequence DNA.
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4.
  • Anvret, A, et al. (författare)
  • Possible involvement of a mitochondrial translation initiation factor 3 variant causing decreased mRNA levels in Parkinson's disease.
  • 2010
  • Ingår i: Parkinson's disease. - 2042-0080. ; 2010
  • Tidskriftsartikel (refereegranskat)abstract
    • Genes important for mitochondrial function have been implicated in Parkinson's disease (PD). Mitochondrial translation initiation factor 3 (MTIF3) is a nuclear encoded protein required for the initiation of complex formation on mitochondrial ribosomes. Dysfunction of MTIF3 may impair mitochondrial function and dopamine neurons appear to be particularly vulnerable to oxidative stress, which may relate to their degeneration in PD. An association was recently reported between the synonymous rs7669(C>T) in MTIF3 and PD in a German case-control material. We investigated rs7669 in a Swedish Parkinson case-control material. The study revealed no significant association of the individual genotypes or alleles with PD. When comparing the combined TT/CT-genotypes versus the CC-genotype, we observed a significant association (P = .0473) with PD. We also demonstrated that the TT-genotype causes a significant decrease in MTIF3 mRNA expression compared to the CC-genotype (P = .0163). Our findings support the hypothesis that MTIF3 may be involved in the etiology of PD.
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5.
  • Belin, AC, et al. (författare)
  • Association study of two genetic variants in mitochondrial transcription factor A (TFAM) in Alzheimer's and Parkinson's disease.
  • 2007
  • Ingår i: Neuroscience letters. - 0304-3940. ; 420:3, s. 257-62
  • Tidskriftsartikel (refereegranskat)abstract
    • Mitochondrial (mt) dysfunction has been implicated in Alzheimer's (AD) and Parkinson's disease (PD). Mitochondrial transcription factor A (TFAM) is needed for mtDNA maintenance, regulating mtDNA copy number and is absolutely required for transcriptional initiation at mtDNA promoters. Two genetic variants in TFAM have been reported to be associated with AD in a Caucasian case-control material collected from Germany, Switzerland and Italy. One of these variants was reported to show a tendency for association with AD in a pooled Scottish and Swedish case-control material and the other variant was reported to be associated with AD in a recent meta-analysis. We investigated these two genetic variants, rs1937 and rs2306604, in an AD and a PD case-control material, both from Sweden and found significant genotypic as well as allelic association to marker rs2306604 in the AD case-control material (P=0.05 and P=0.03, respectively), where the A-allele appears to increase risk for developing AD. No association was observed for marker rs1937. We did not find any association in the PD case-control material for either of the two markers. The distribution of the two-locus haplotype frequencies (based on rs1937 and rs2306604) did not differ significantly between affected individuals and controls in the two sample sets. However, the global P-value for haplotypic association testing indicated borderline association in the AD sample set. Our data suggests that the rs2306604 A-allele could be a moderate risk factor for AD, which is supported by the recent meta-analysis.
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6.
  • Belin, AC, et al. (författare)
  • Leucine-rich repeat kinase 2 (LRRK2) mutations in a Swedish Parkinson cohort and a healthy nonagenarian.
  • 2006
  • Ingår i: Movement disorders : official journal of the Movement Disorder Society. - 0885-3185. ; 21:10, s. 1731-4
  • Tidskriftsartikel (refereegranskat)abstract
    • Specific variants of Leucine-rich repeat kinase 2 (LRRK2) have been shown to associate with Parkinson's disease (PD). Several mutations have been found in PD populations from different parts of the world. We investigated the occurrence of three mutations (R1441G/C/H, G2019S, and I2020T) in our Swedish case-control material and identified four carriers of the G2019S mutation in 284 PD cases and 1 95-year-old carrier in 305 controls. The other two variants were absent in our material. We conclude that the LRRK2 G2019S mutation constitutes a significant factor for PD in the Swedish population and that it is not completely penetrant.
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7.
  • Johnning, Anna, 1985-, et al. (författare)
  • The resistomes of six carbapenem-resistant pathogens - a critical genotype-phenotype analysis
  • 2018
  • Ingår i: Microbial Genomics. - 2057-5858. ; 4:11
  • Tidskriftsartikel (refereegranskat)abstract
    • Carbapenem resistance is a rapidly growing threat to our ability to treat refractory bacterial infections. To understand how carbapenem resistance is mobilized and spread between pathogens, it is important to study the genetic context of the underlying resistance mechanisms. In this study, the resistomes of six clinical carbapenem-resistant isolates of five different species - Acinetobacter baumannii, Escherichia coli, two Klebsiella pneumoniae, Proteus mirabilis and Pseudomonas aeruginosa - were characterized using whole genome sequencing. All Enterobacteriaceae isolates and the A. baumannii isolate had acquired a large number of antimicrobial resistance genes (7-18 different genes per isolate), including the following encoding carbapenemases: blaKPC-2, blaOXA-48, blaOXA-72, blaNDM-1, blaNDM-7 and blaVIM-1. In addition, a novel version of blaSHV was discovered. Four new resistance plasmids were identified and their fully assembled sequences were verified using optical DNA mapping. Most of the resistance genes were co-localized on these and other plasmids, suggesting a risk for co-selection. In contrast, five out of six carbapenemase genes were present on plasmids with no or few other resistance genes. The expected level of resistance - based on acquired resistance determinants - was concordant with measured levels in most cases. There were, however, several important discrepancies for four of the six isolates concerning multiple classes of antibiotics. In conclusion, our results further elucidate the diversity of carbapenemases, their mechanisms of horizontal transfer and possible patterns of co-selection. The study also emphasizes the difficulty of using whole genome sequencing for antimicrobial susceptibility testing of pathogens with complex genotypes.
8.
  • Westerlund, Anna, 1978-, et al. (författare)
  • Facilitating system-wide organizational change in health care
  • 2015
  • Ingår i: International Journal of Quality and Service Sciences. - Emerald Group Publishing Limited. - 1756-669X. ; 7:1, s. 72-89
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: The purpose of this paper was to investigate the role of an intra-organizational change facilitating function (CFF) in relation to a multi-level development initiative in a health care organization. Involved actors’ views on factors in need of attention and how the CFF related to these factors were studied.Design/methodology/approach: A longitudinal case study design was used, combining data from questionnaires, process diaries and interviews with employees at the CFF, managers and clinic staff.Findings: Factors on micro, meso and macro levels, crucial to attend to, were highlighted by respondents at staff and managerial levels. The CFF related to some of these factors by acting upon them, or by developing plans to handle them, while other factors were unattended to. The CFF activities also had indirect influence on other factors. The CFF role and responsibilities were not clearly defined beforehand, and a need to clarify a division of roles and responsibilities is highlighted.Research limitations/implications: Our study contributes to current knowledge on facilitation of change by relating it to an organizational dimension of implementation.Practical implications: The description of important factors to handle during a large organizational change process and issues a CFF can encounter may aid others involved in designing and managing large organizational development initiatives.Originality/value:The study elaborates on less studied functions and roles of an intra-organizational CFF in relation to factors of vital importance for organizational change and development in health-care organizations.
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9.
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10.
  • Westerlund, Anna, 1978- (författare)
  • The role of implementation science in healthcare improvement efforts investigating three complex interventions
  • 2018
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • For decades, scholars have found significant gaps between the knowledge available and the knowledge applied in healthcare. Many potential benefits of adequate knowledge based interventions are therefore never achieved. A considerable body of knowledge has evolved on how to promote a better uptake of evidence-based knowledge into routine use. Even so, the actual impact and usefulness of implementation research findings among healthcare practitioners have not been extensively studied.Accordingly, the overall aim of this thesis is to contribute to the understanding of how the implementation of complex interventions into healthcare can be improved. This is done by investigating whether some of these efforts do correspond with available scientific knowledge on implementation.The thesis is based on three cases contributing to four studies. The cases studied are: the National Perinatal Patient Safety program (NPPS), the Dynamic and Viable Organisation initiative (DVO), and the International Child Development Program (ICDP). All studies focuses on the early stages of implementation.A mixed methods approach was adopted, involving both qualitative and quantitative methods. Data collection consisted of interviews, questionnaires, observations, and process diaries. Qualitative content analysis (conventional and directed), descriptive and non-parametric statistics were used. The focus was on implementation strategies used by healthcare actors in relation to factors influencing implementation processes and outcomes. More specifically, healthcare actors perspectives on such factors and whether they were addressed by the strategies used, was investigated. A process evaluation of implementation outcomes was also part of the thesis.The healthcare actors in focus were the adopters, i.e. practitioners expected to change their work practices, and implementation facilitators. The latter refer to actors with a more or less explicit responsibility to implement new practices or interventions aimed at improving the quality and effectiveness of the provided health services.Variation was found regarding how the implementation strategies used in the three cases corresponded with available scientific knowledge on implementation. In Case NPPS, the implementation facilitators planned, designed, and ensured that the core interventions of the implementation strategy were executed in a rational manner. Several important implementation factors were addressed by the strategy. The process evaluation of effects on readiness for change by the development of a team mental model among adopters showed positive results.In Case DVO a strategy was used that evolved over time, partly based on raised questions and feedback from staff and managers involved. The strategy can be described as an intuitive ‘socially accomplished activity’. This strategy involved addressing ‘Implementation Process-related factors’ in order to affect motivation and increase the tension for change among adopters.In Case ICDP, the results reflected a shortage of strategies during the early stage of implementation. The main intervention was the stepwise ICDP-education. A more comprehensive implementation strategy covering implementation factors highlighted as important among adopters was not developed. The process evaluation revealed vague directives on what was expected regarding the use and adaptation of ICDP to current practice versus preservation of fidelity to the original ICDP. This situation resulted in a rather large variation in how the changes in work practices were perceived among the health centres involved. No health centre practiced ICDP in its original form.A new knowledge-practice gap is discussed based on the findings in this thesis: a gap between the scientific knowledge on implementation and the actual implementation strategies used in practice during improvement efforts initiated by healthcare actors. The findings show that correspondence between scientific knowledge on implementation and what is actually done in order to accomplish change in practice might be more random (or implicit) than systematic. The question of how to transfer scientific knowledge on implementation into user-friendly resources for practitioners is discussed. A tentative model is suggested, which contributes to existing determinant frameworks by focusing on relations among factors. The model may be used in healthcare practice, to guide the design of an implementation strategy (or as a pathway for tailored implementation interventions) and aid the assignment of responsibilities in relation to factors that are known to affect implementation processes and outcomes.The question of how to transfer models and frameworks into user-friendly resources needs further attention. It is suggested that action oriented research aiming at further developing and establishing the concept of ‘practical implementation science’ should be conducted. This could be a way of bridging the knowledge-practice gap in healthcare.
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