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- Almstedt, Karin, 1980-, et al.
(author)
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Amyloid fibrils of human prion protein are spun and woven from morphologically disordered aggregates
- 2009
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In: Prion. - Austin : Landes Bioscience Journals. - 1933-6896 .- 1933-690X. ; 3:4, s. 224-235
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Journal article (peer-reviewed)abstract
- Propagation and infectivity of prions in human prionopathies are likely associated with conversion of the mainly α-helical human prion protein, HuPrP, into an aggregated form with amyloid-like properties. Previous reports on efficient conversion of recombinant HuPrP have used mild to harsh denaturing conditions to generate amyloid fibrils in vitro. Herein we report on the in vitro conversion of four forms of truncated HuPrP (sequences 90-231 and 121-231 with and without an N-terminal hexa histidine tag) into amyloid-like fibrils within a few hours by using a protocol (phosphate buffered saline solutions at neutral pH with intense agitation) close to physiological conditions. The conversion process monitored by thioflavin T, ThT, revealed a three stage process with lag, growth and equilibrium phases. Seeding with preformed fibrils shortened the lag phase demonstrating the classic nucleated polymerization mechanism for the reaction. Interestingly, comparing thioflavin T kinetics with solubility and turbidity kinetics it was found that the protein initially formed non-thioflavionophilic, morphologically disordered aggregates that over time matured into amyloid fibrils. By transmission electron microscopy and by fluorescence microscopy of aggregates stained with luminescent conjugated polythiophenes (LCPs); we demonstrated that HuPrP undergoes a conformational conversion where spun and woven fibrils protruded from morphologically disordered aggregates. The initial aggregation functioned as a kinetic trap that decelerated nucleation into a fibrillation competent nucleus, but at the same time without aggregation there was no onset of amyloid fibril formation. The agitation, which was necessary for fibril formation to be induced, transiently exposes the protein to the air-water interface suggests a hitherto largely unexplored denaturing environment for prion conversion.
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| 4. |
- Axelsson, Ann-Sofie, 1967, et al.
(author)
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Taking a New Direction: Behavioral Interventions in Higher Education supported by Ajzen’s Theory of Planned Behavior
- 2010
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In: Engineering Education in Sustainable Development (EESD10), Gothenburg, Sweden, September 19-22, 2010.
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Conference paper (other academic/artistic)abstract
- According to Ajzen [1], intentions to perform behaviors of various kinds can be predicted on the basis of attitudes towards the behavior, subjective norms, and perceived behavioral control. In the light of this theory a several weeks long exercise within six higher education courses was conducted, in order to support the students to take a new direction in their every day lives in terms of carrying out sustainable and self-imposed actions such as decreasing the use of energy in the household and eating lower on the food chain. An online questionnaire was distributed in order to find out how effective this exercise was, what the key operational mechanisms in the exercise were, and if this exercise made an impact on other areas than the one selected for this course. An analysis showed that a majority of the students perceived the exercise inspiring and motivating, supporting change of behavior in the intended, new direction. There were, however, a number of suggestions for improvement, to be seriously considered for future implementation. For example, there seems to be a need for clarifying the relevance of the task for future engineering work life. The two key operational mechanisms identified were the individual’s own attitude towards the specific behaviour and the perception that the task was within their control. A further analysis also showed that half of the students still carried out the sustainable actions after 3 months to up to 2 years and that a considerable part of them had changed their behavior within other areas. This study shows that this type of behavioral change, within a course curriculum, is very effective, and that formative research, with Ajzen's theoretical framework as a foundation, could be a starting point for this to happen.
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| 5. |
- Bagheri, Maryam, et al.
(author)
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Amyloid Beta1-40-Induced Astrogliosis and the Effect of Genistein Treatment in Rat: A Three-Dimensional Confocal Morphometric and Proteomic Study
- 2013
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In: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 8:10
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Journal article (peer-reviewed)abstract
- Astrocytes are highly involved in regulation and homeostasis of the extracellular environment in the healthy brain. In pathological conditions, these cells play a major role in the inflammatory response seen in CNS tissues, which is called reactive astrogliosis and includes hypertrophy and proliferation of astrocytes. Here, we performed 3D confocal microscopy to evaluate the morphological response of reactive astrocytes positive for glial fibrillary acidic protein (GFAP) in rats, to the presence of Aβ1–40 in the rat brain before and after treatment with genistein. In 50 astrocytes per animal, we measured the volume and surface area for the nucleus, cell body, the entire cell, the tissue covered by single astrocytes and quantified the number and length of branches, the density of the astrocytes and the intensity of GFAP immunoreactivity. Injecting Aβ1–40 into the brain of rats caused astrogliosis indicated by increased values for all measured parameters. Mass spectrometric analysis of hippocampal tissue in Aβ1–40-injected brain showed decreased amounts of tubulins, enolases and myelin basic protein, and increased amounts of dihydropyrimidinase-related protein 2. In Aβ1–40-injected rats pretreated with genistein, GFAP intensity was decreased to the sham-operated group level, and Aβ1–40-induced astrogliosis was significantly ameliorated.
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| 6. |
- Borg Hammer, Anne Sofie, et al.
(author)
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Hypodiploidy has unfavorable impact on survival in pediatric acute myeloid leukemia : An I-BFM Study Group collaboration
- 2023
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In: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 7:6, s. 1045-1055
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Journal article (peer-reviewed)abstract
- Hypodiploidy, defined as modal numbers (MNs) 45 or lower, has not been independently investigated in pediatric acute myeloid leukemia (AML) but is a well-described high-risk factor in pediatric acute lymphoblastic leukemia. We aimed to characterize and study the prognostic impact of hypodiploidy in pediatric AML. In this retrospective cohort study, we included children below 18 years of age with de novo AML and a hypodiploid karyotype diagnosed from 2000 to 2015 in 14 childhood AML groups from the International Berlin-Frankfurt-Münster (I-BFM) framework. Exclusion criteria comprised constitutional hypodiploidy, monosomy 7, composite karyotype, and t(8;21) with concurring sex chromosome loss. Hypodiploidy occurred in 81 patients (1.3%) with MNs, 45 (n = 66); 44 (n = 10) and 43 (n = 5). The most frequently lost chromosomes were chromosome 9 and sex chromosomes. Five-year event-free survival (EFS) and overall survival (OS) were 34% and 52%, respectively, for the hypodiploid cohort. Children with MN≤44 (n = 15) had inferior EFS (21%) and OS (33%) compared with children with MN = 45 (n = 66; EFS, 37%; OS, 56%). Adjusted hazard ratios (HRs) were 4.9 (P = .001) and 6.1 (P = .003). Monosomal karyotype or monosomy 9 had particular poor OS (43% and 15%, respectively). Allogeneic stem cell transplantation (SCT) in first complete remission (CR1) (n = 18) did not mitigate the unfavorable outcome of hypodiploidy (adjusted HR for OS was 1.5; P = .42). We identified pediatric hypodiploid AML as a rare subgroup with an inferior prognosis even in the patients treated with SCT in CR1.
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| 7. |
- Borssén, Magnus, et al.
(author)
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DNA Methylation Adds Prognostic Value to Minimal Residual Disease Status in Pediatric T-Cell Acute Lymphoblastic Leukemia
- 2016
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In: Pediatric Blood & Cancer. - : Wiley. - 1545-5009 .- 1545-5017. ; 63:7, s. 1185-1192
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Journal article (peer-reviewed)abstract
- Background. Despite increased knowledge about genetic aberrations in pediatric T-cell acute lymphoblastic leukemia (T-ALL), no clinically feasible treatment-stratifying marker exists at diagnosis. Instead patients are enrolled in intensive induction therapies with substantial side effects. In modern protocols, therapy response is monitored by minimal residual disease (MRD) analysis and used for postinduction risk group stratification. DNA methylation profiling is a candidate for subtype discrimination at diagnosis and we investigated its role as a prognostic marker in pediatric T-ALL. Procedure. Sixty-five diagnostic T-ALL samples from Nordic pediatric patients treated according to the Nordic Society of Pediatric Hematology and Oncology ALL 2008 (NOPHO ALL 2008) protocol were analyzed by HumMeth450K genome wide DNA methylation arrays. Methylation status was analyzed in relation to clinical data and early T-cell precursor (ETP) phenotype. Results. Two distinct CpG island methylator phenotype (CIMP) groups were identified. Patients with a CIMP-negative profile had an inferior response to treatment compared to CIMP-positive patients (3-year cumulative incidence of relapse (CIR3y) rate: 29% vs. 6%, P = 0.01). Most importantly, CIMP classification at diagnosis allowed subgrouping of high-risk T-ALL patients (MRD >= 0.1% at day 29) into two groups with significant differences in outcome (CIR3y rates: CIMP negative 50% vs. CIMP positive 12%; P = 0.02). These groups did not differ regarding ETP phenotype, but the CIMP-negative group was younger (P = 0.02) and had higher white blood cell count at diagnosis (P = 0.004) compared with the CIMP-positive group. Conclusions. CIMP classification at diagnosis in combination with MRD during induction therapy is a strong candidate for further risk classification and could confer important information in treatment decision making.
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| 8. |
- Brunklaus, Birgit, 1970-, et al.
(author)
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Carbon theatre in public spaces : Using participatory theatre and co-designmethods in a museum for shaping lowcarbon lifestyles
- 2019
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In: Life Cycle Management Conference 2019. - Poznan, Polen.
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Conference paper (peer-reviewed)abstract
- Over the past ten years, the need for public spaces to deal with burning societal issues, such as climate change, has become even more important. Participatory theatre offers ways to meet the longing for shared forums by engaging large groups of people in exploring difficult social dilemmas. It can potentially empower participants to change their own situations and organizations. In a previous design research project Quantifying your carbon footprint, this gap was in focus. We will use the findings from the Quantifying carbon footprint project as an entry point and expand it with Life Cycle Assessment (LCA) on objects from the current museum collection and on daily life activities that have a carbon impact. The goal of the project is to explore and understand the climate and environmental impacts of lifestyles. The method used here are participatory theatre and co-design methods and pop-up exhibitions are used to engage young citizens in negotiating social norms and understanding their possible impact on CO2 emissions. The museum collections play a crucial role in the process of understanding how LCA calculations are related to mundane objects and reflecting on the temporality of social norms that are negotiated and re-negotiated through the way we handle products and objects in our everyday life. Developing new practices for museums involving participatory methods in order to engage young citizens in climate research. The results of the introductory meeting and study visit show that using the museum’s collection, the history and the value of things in the past centuries become clear and easier to reflect on compared to today’s unsustainable lifestyle – travelling and over consumption. Carbon Dioxide Theatre is an attempt to shape a shared space on a local level, in line with the priorities of the museum’s three years plan.
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| 9. |
- Bäck, Marcus, et al.
(author)
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Tyrosine Side-Chain Functionalities at Distinct Positions Determine the Chirooptical Properties and Supramolecular Structures of Pentameric Oligothiophenes
- 2020
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In: ChemistryOpen. - : Wiley. - 2191-1363. ; 9:11, s. 1100-1108
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Journal article (peer-reviewed)abstract
- Control over the photophysical properties and molecular organization of pi-conjugated oligothiophenes is essential to their use in organic electronics. Herein we synthesized and characterized a variety of anionic pentameric oligothiophenes with different substitution patterns of L- or D-tyrosine at distinct positions along the thiophene backbone. Spectroscopic, microscopic, and theoretical studies of L- or D-tyrosine substituted pentameric oligothiophene conjugates revealed the formation of optically active pi-stacked self-assembled aggregates under acid conditions. The distinct photophysical characteristics, as well as the supramolecular structures of the assemblies, were highly influenced by the positioning of the L- or D-tyrosine moieties along the thiophene backbone. Overall, the obtained results clearly demonstrate how fundamental changes in the position of the enantiomeric side-chain functionalities greatly affect the optical properties as well as the architecture of the self-assembled supramolecular structures.
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