| 1. |
- Almstedt, Karin, 1980-, et al.
(författare)
-
Amyloid fibrils of human prion protein are spun and woven from morphologically disordered aggregates
- 2009
-
Ingår i: Prion. - Austin : Landes Bioscience Journals. - 1933-6896 .- 1933-690X. ; 3:4, s. 224-235
-
Tidskriftsartikel (refereegranskat)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.
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
- Axelsson, Ann-Sofie, 1967, et al.
(författare)
-
Taking a New Direction: Behavioral Interventions in Higher Education supported by Ajzen’s Theory of Planned Behavior
- 2010
-
Ingår i: Engineering Education in Sustainable Development (EESD10), Gothenburg, Sweden, September 19-22, 2010.
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)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.
|
|
| 5. |
- Bagheri, Maryam, et al.
(författare)
-
Amyloid Beta1-40-Induced Astrogliosis and the Effect of Genistein Treatment in Rat: A Three-Dimensional Confocal Morphometric and Proteomic Study
- 2013
-
Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 8:10
-
Tidskriftsartikel (refereegranskat)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.
|
|
| 6. |
- Borg Hammer, Anne Sofie, et al.
(författare)
-
Hypodiploidy has unfavorable impact on survival in pediatric acute myeloid leukemia : An I-BFM Study Group collaboration
- 2023
-
Ingår i: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 7:6, s. 1045-1055
-
Tidskriftsartikel (refereegranskat)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.
|
|
| 7. |
- Borssén, Magnus, et al.
(författare)
-
DNA Methylation Adds Prognostic Value to Minimal Residual Disease Status in Pediatric T-Cell Acute Lymphoblastic Leukemia
- 2016
-
Ingår i: Pediatric Blood & Cancer. - : Wiley. - 1545-5009 .- 1545-5017. ; 63:7, s. 1185-1192
-
Tidskriftsartikel (refereegranskat)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.
|
|
| 8. |
- Brunklaus, Birgit, 1970-, et al.
(författare)
-
Carbon theatre in public spaces : Using participatory theatre and co-designmethods in a museum for shaping lowcarbon lifestyles
- 2019
-
Ingår i: Life Cycle Management Conference 2019. - Poznan, Polen.
-
Konferensbidrag (refereegranskat)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.
|
|
| 9. |
- Bäck, Marcus, et al.
(författare)
-
Tyrosine Side-Chain Functionalities at Distinct Positions Determine the Chirooptical Properties and Supramolecular Structures of Pentameric Oligothiophenes
- 2020
-
Ingår i: ChemistryOpen. - : Wiley. - 2191-1363. ; 9:11, s. 1100-1108
-
Tidskriftsartikel (refereegranskat)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.
|
|
| 10. |
|
|
| 11. |
|
|
| 12. |
|
|
| 13. |
- Danielsson, Anna, et al.
(författare)
-
Science identities: A systematic review of a consolidating field
- 2021
-
Konferensbidrag (refereegranskat)abstract
- This paper presents a systematic review of research on learner identities within science education research. The purpose is to identify different methodological approaches in the field of science identities research, the prevalence of the approaches, and their strengths and weaknesses as well as to identify key challenges and fruitful future developments. In an open, thematic analyses of 190 papers, located through Web of Science searches, we identify three different methodological approaches; macro-studies within a psychological tradition (30 studies), macro-studies within a sociological tradition (20 studies), and micro-studies within an interpretivist tradition (131 studies) (9 papers are not empirical studies). Consequently, this field is dominated by small-scale, qualitative case studies, in accordance with what has been found in previous reviews. Yet, this field is also found to be conceptually diverse, with the notion of identity used broadly, sometimes theorised as a perspective, and sometimes used to denote an empirical phenomena. In moving the field further, we argue that it would be beneficial to establish a stronger theoretical and conceptual coherence, thereby aiding the building of cumulative knowledge across studies. Further, we also see an increased attentiveness to scaling as a key for making impact; both regarding small-scale qualitative studies being scaled up to broader groups of students and educators and large-scale quantitative studies being scaled down for the use of individual teachers.
|
|
| 14. |
- Danielsson, Anna T., et al.
(författare)
-
The identity turn in science education research: a critical review of methodologies in a consolidating field : A critical review of methodologies in a consolidating field
- 2023
-
Ingår i: Cultural Studies of Science Education. - : Springer Nature. - 1871-1502 .- 1871-1510.
-
Tidskriftsartikel (refereegranskat)abstract
- This manuscript reflects on the affordances and limitations of methodological approaches commonly adopted by science education researchers examining learner identities. Our aims are to unpack the relative strengths and weaknesses of such approaches and note their respective prevalence. In so doing, we identify and critique studies which we consider exemplify the different approaches and, in turn, note the direction of fruitful developments and the nature of key challenges. From our review of the field, we suggest that three discrete methodological approaches can be identified: macro-studies within a psychological tradition; macro-studies within a sociological tradition; and micro-studies within an interpretive tradition. Our review comprised a critical analysis of papers included in the Web of Science databases published between 1998 and 2018. A total of 198 papers examining aspects of learner identity relating to science were identified. Of these, the majority (146) were categorised as micro-studies within an interpretive tradition. We discuss the implications of methodological choices for the advancement of understanding and further note ambiguities in the field particularly in relation to the ways in which learner identity research is conceived. We also raise questions for the field relating to the ways in which findings may be scaled, and how the field might develop to allow stronger theoretical and conceptual coherence.
|
|
| 15. |
- Danielsson, Anna T., Professor, 1978-, et al.
(författare)
-
Young Peoples’ Online Science Practices as a Gateway to Higher Education STEM
- 2023
-
Ingår i: Research in science education. - : Springer Science and Business Media LLC. - 0157-244X .- 1573-1898. ; 53:4, s. 759-770
-
Tidskriftsartikel (refereegranskat)abstract
- The purpose of this manuscript is to explore how students perceive that online practices have enabled their participation in university physics programmes. In order to conceptualise how students bridge their science participation across physical and online spaces, we make use of the learning ecology perspective. This perspective is complemented with the notion of science capital, analysing how students have been able to strengthen different aspects of science capital through online participation. Data has been generated through semi-structured interviews guided by a timeline, constructed in collaboration between the interviewer and the interviewee. Twenty-one students enrolled in higher education physics have been interviewed, with a focus on their trajectories into higher education physics. The findings focus on four students who in various ways all have struggled to access science learning resources and found ways to utilise online spaces as a complement to their physical learning ecologies. In the manuscript, we show how online practices have contributed to the students’ learning ecologies, e.g. in terms of building networks and functioning as learning support, and how resources acquired through online science practices have both use and exchange value in the wider science community. Online science participation is thus both curiosity driven and founded in instrumental reasons (using online tutoring to pass school science). Furthermore, we argue that online spaces have the potential to offer opportunities for participation and network building for students who do not have access to science activities and science people in their everyday surroundings.
|
|
| 16. |
|
|
| 17. |
- Danielsson, Anna, et al.
(författare)
-
The exceptional physics girls – grown up
- 2021
-
Konferensbidrag (refereegranskat)abstract
- This paper focus on the identity trajectories of eleven female students enrolled in higher education physics, with a particular focus on how they have acquired and mobilized resources during their trajectories. We are also interested in what has made higher education physics possible for students who enrol in such educations despite limited opportunities to accumulate valued forms of science capital. The study draws on interviews with 20 (11 women/9 men) first- and second-year university physics students. The interviews are inspired by life history interviews and structured around the construction of a ‘time line’. In the preliminary analysis we have we have discerned two different trajectories into higher education physics; ’The high achiever trajectory’ (characterized by general high achievement in school and ’The natural physicist trajectory’ (characterized by interest in and identification with a particular area of physics or a particular purpose with the physics education, rather than continuous academic high achievement). Across both trajectories the interviewed women can be understood as ‘exceptional’ in various ways. In particular the students’ accumulation of science related social capital stands out and it is noticeable how it extends far beyond the family. The accumulation of science related social capital is connected to the furthering of high-level scientific literacy and a deepened knowledge of how the science community works, showing how different aspects of science capital are inter-related and can re-inforce one another
|
|
| 18. |
- Danielsson, Anna, Professor, 1978-, et al.
(författare)
-
The identity turn in science education research : a critical review of methodologies in a consolidating field
- 2023
-
Ingår i: Cultural Studies of Science Education. - : Springer Science and Business Media LLC. - 1871-1502 .- 1871-1510. ; :18, s. 695-754
-
Forskningsöversikt (refereegranskat)abstract
- This manuscript reflects on the affordances and limitations of methodological approaches commonly adopted by science education researchers examining learner identities. Our aims are to unpack the relative strengths and weaknesses of such approaches and note their respective prevalence. In so doing, we identify and critique studies which we consider exemplify the different approaches and, in turn, note the direction of fruitful developments and the nature of key challenges. From our review of the field, we suggest that three discrete methodological approaches can be identified: macro-studies within a psychological tradition; macro-studies within a sociological tradition; and micro-studies within an interpretive tradition. Our review comprised a critical analysis of papers included in the Web of Science databases published between 1998 and 2018. A total of 198 papers examining aspects of learner identity relating to science were identified. Of these, the majority (146) were categorised as micro-studies within an interpretive tradition. We discuss the implications of methodological choices for the advancement of understanding and further note ambiguities in the field particularly in relation to the ways in which learner identity research is conceived. We also raise questions for the field relating to the ways in which findings may be scaled, and how the field might develop to allow stronger theoretical and conceptual coherence.
|
|
| 19. |
- Danielsson, Anna, et al.
(författare)
-
Young peoples’ online science practices as a gateway to higher education STEM
- 2022
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The purpose of this presentation is to explore how students perceive that online practices have enabled their participation in university physics programmes. The presentation is part of a larger project, exploring students’ trajectories to higher education physics, with a particular focus on students from under-represented groups. In order to conceptualise how students bridge their science participation across physical and online spaces we make use of the learning ecology perspective (Barron 2006). This perspective is complemented with the notion of science capital (Archer et al. 2015), analysing how students have been able to strengthen different aspects of science capital through online participation. Data has been generated through semi-structured interviews guided by a timeline, constructed in collaboration between the interviewer and the interviewee. 20 students enrolled in higher education physics have been interviewed, with a focus on their trajectories into higher education physics. The findings focus on five students who in various ways all have struggled to access science learning resources and found ways to utilise online spaces as a complement to their physical learning ecologies. In the presentation we show how online practices have contributed to the students’ learning ecologies, e.g. in terms of building networks and functioning as learning support, and how resources acquired through online science practices have both use and exchange value in the wider science community (Gonsalves et al. 2021).Online science participation is thus both curiosity driven and founded in instrumental reasons (using online tutoring to pass school science). Further, we argue that online spaces have the potential to offer opportunities for participation and network building for students who do not have access to science activities and science people in their everyday surroundings. However, this is not to say that online activities are equally and fairly accessible to all, and the potential gendering of online activities will be discussed in the presentation. Archer, L., Dawson, E., DeWitt, J., Seakins, A., & Wong, B. (2015). “Science capital”: A conceptual, methodological, and empirical argument for extending bourdieusian notions of capital beyond the arts. Journal of research in science teaching, 52(7), 922-948. Barron, B. (2006). Interest and self-sustained learning as catalysts of development: A learning ecology perspective. Human development, 49(4), 193-224. Gonsalves, A. J., Cavalcante, A. S., Sprowls, E. D., & Iacono, H. (2021). “Anybody can do science if they’re brave enough”: Understanding the role of science capital in science majors’ identity trajectories into and through postsecondary science. Journal of Research in Science Teaching, 58(8), 1117–1151
|
|
| 20. |
|
|
| 21. |
- El Gohary, Fouad, et al.
(författare)
-
Identifying Challenges in Engaging Users to Increase Self-Consumption of Electricity in Microgrids
- 2021
-
Ingår i: Energies. - : MDPI AG. - 1996-1073. ; 14:5
-
Tidskriftsartikel (refereegranskat)abstract
- A microgrid's self-consumption rate reflects its ability to retain its own energy and decrease its reliance on the synchronous grid. This paper investigates the empirical case of a microgrid equipped with photovoltaic (PV) panels and identifies challenges in engaging the microgrid's users to increase their self-consumption. Accordingly, we explored both the physical and social dimensions of the microgrid. The former involved mapping the electricity consumption and production through an exploratory data analysis, and evaluating the associated price signals, while the latter involved the use of design interventions to explore users' perceptions of the system. We highlight the problem of price signal impedance, the need for cost reflective pricing and the challenge in designing and extending internal price models in settings with various actors. We address the limitations of price signals, alongside alternative unidimensional signals, and emphasize the need for an integrated approach to a user engagement strategy as well as the challenges that this approach entails. Our results shed light on the complexity of energy communities such as microgrids, and why their implementation can introduce multidimensional challenges that demand cross-disciplinary approaches.
|
|
| 22. |
- Ellingsen, Pal Gunnar, et al.
(författare)
-
Spectral correlation analysis of Amyloid beta plaque inhomogeneity from double staining experiments
- 2013
-
Ingår i: Journal of Biomedical Optics. - : Society of Photo-optical Instrumentation Engineers (SPIE). - 1083-3668 .- 1560-2281. ; 18:10
-
Tidskriftsartikel (refereegranskat)abstract
- A spectral correlation algorithm for the analysis of hyperspectral fluorescence images is proposed by Ellingsen et al. [J. Biomed. Opt. 18, 020501 (2013)]. Here, it is applied to the analysis of double-stained A beta amyloid plaques being related to the Alzheimers disease (AD). Sections of APP/PS1 AD mice model brains are double stained with luminescent-conjugated oligothiophenes, known to bind to amyloid protein deposits. Hyperspectral fluorescence images of the brain sections are recorded and by applying the correlation algorithm the spectral inhomogeneity of the double-stained samples is mapped in terms of radial distribution and spectral content. To further investigate the progression of A beta amyloid plaque formation, 19 AD mice of different ages up to 23 months are characterized, enabling a statistical analysis of the plaque heterogeneity. In accordance with recent findings by Nystrom et al. [ACS Chem. Biol. 8, 1128-1133 (2013)], the spectral distribution within A beta plaques is found to vary with age throughout the lifespan of the mouse. With the new correlation algorithm, it is possible to quantify the spectral abundance of the two stains depending on the relative distance from the plaque center and mouse age. Thus, we demonstrate the use of the correlation analysis approach in double-staining experiments and how it is possible to relate these to structural/spectral changes in biological samples. (C) The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.
|
|
| 23. |
- Fändrich, M., et al.
(författare)
-
Amyloid fibril polymorphism: a challenge for molecular imaging and therapy
- 2018
-
Ingår i: Journal of Internal Medicine. - : WILEY. - 0954-6820 .- 1365-2796. ; 283:3, s. 218-237
-
Tidskriftsartikel (refereegranskat)abstract
- The accumulation of misfolded proteins (MPs), both unique and common, for different diseases is central for many chronic degenerative diseases. In certain patients, MP accumulation is systemic (e.g. TTR amyloid), and in others, this is localized to a specific cell type (e.g. Alzheimers disease). In neurodegenerative diseases, NDs, it is noticeable that the accumulation of MP progressively spreads throughout the nervous system. Our main hypothesis of this article is that MPs are not only markers but also active carriers of pathogenicity. Here, we discuss studies from comprehensive molecular approaches aimed at understanding MP conformational variations (polymorphism) and their bearing on spreading of MPs, MP toxicity, as well as MP targeting in imaging and therapy. Neurodegenerative disease (ND) represents a major and growing societal challenge, with millions of people worldwide suffering from Alzheimers or Parkinsons diseases alone. For all NDs, current treatment is palliative without addressing the primary cause and is not curative. Over recent years, particularly the shape-shifting properties of misfolded proteins and their spreading pathways have been intensively researched. The difficulty in addressing ND has prompted most major pharma companies to severely downsize their nervous system disorder research. Increased academic research is pivotal for filling this void and to translate basic research into tools for medical professionals. Recent discoveries of targeting drug design against MPs and improved model systems to study structure, pathology spreading and toxicity strongly encourage future studies along these lines to provide an opportunity for selective imaging, prognostic diagnosis and therapy.
|
|
| 24. |
- Gallardo, Rodrigo, et al.
(författare)
-
De novo design of a biologically active amyloid
- 2016
-
Ingår i: Science. - : AMER ASSOC ADVANCEMENT SCIENCE. - 0036-8075 .- 1095-9203. ; 354:6313, s. 720-
-
Tidskriftsartikel (refereegranskat)abstract
- Most human proteins possess amyloidogenic segments, but only about 30 are associated with amyloid-associated pathologies, and it remains unclear what determines amyloid toxicity. We designed vascin, a synthetic amyloid peptide, based on an amyloidogenic fragment of vascular endothelial growth factor receptor 2 (VEGFR2), a protein that is not associated to amyloidosis. Vascin recapitulates key biophysical and biochemical characteristics of natural amyloids, penetrates cells, and seeds the aggregation of VEGFR2 through direct interaction. We found that amyloid toxicity is observed only in cells that both express VEGFR2 and are dependent on VEGFR2 activity for survival. Thus, amyloid toxicity here appears to be both protein-specific and conditional-determined by VEGFR2 loss of function in a biological context in which target protein function is essential.
|
|
| 25. |
|
|
| 26. |
- Gonsalves, Allison J., et al.
(författare)
-
Other spaces for young pople's identity work in physics: resources accessed through informal physics education in Sweden
- 2022
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- For students from minoritized backgrounds in physics, especially White and racialized women and students from working class backgrounds, inbound identity trajectories into physics are generally regarded as exceptional. In this study, we investigate the experiences that minoritized students have which may support their sustained interest and achievement in physics, and their ongoing inbound trajectories into post-secondary physics education. To understand these experiences, in this presentation we look to the role of informal physics education (IPE) programs as “other spaces” which can offer resources that support students’ development of practice-linked identities. This study collected timeline interview data from 21 students enrolled in post-secondary physics programs in Sweden. In this presentation, we draw on data collected from 7 of these participants, all of them young women in their first year of physics at universities across Sweden. In the analysis we identify the various forms of resources made available through IPE learning contexts, and how these create possibilities for young people to engage in forms of identity work that contribute to the construction of new possible selves in physics. Findings suggest that students can access important relational and ideational resources through IPE programs. Relational resources included a) supportive social networks; b) enduring relationships; and c) relatability. Ideational resources emerged as: a) sources of information which possibilized physics for participants; b) information that provided possibilities to learn about the life of a physicist; and c) important sources of recognition for participants seeking membership in the field. We argue that these resources are critical to support participants’ potential to disrupt the dominant narratives among young women that “physics is not for me” (Archer et al., 2020). Rather, IPE opportunities can support the imagination of “possible selves” in physics (Markus & Nurius, 1986). However, while we highlight the importance that IPE experiences play in the lives of young people in physics, we also discuss that these kinds of experiences remain inaccessible to most students, and thus reproduce a certain elitism in the field. This presentation will conclude with a discussion of how the relative inaccessibility of IPE experiences can preserve dominant relations in physics, and may do more to obscure social inequalities than it does to repair them. Archer, L., Moote, J., and MacLeod, E. (2020). Learning That Physics Is ‘Not for Me’: Pedagogic Work and the Cultivation of Habitus among Advanced Level Physics Students, Journal of the Learning Sciences. 29, 3, 347-384. Markus, H., & Nurius, P. (1986). Possible selves. American psychologist, 41(9), 954.
|
|
| 27. |
- Gonsalves, Allison J., et al.
(författare)
-
Other spaces for young women's identity work in physics: Resources accessed through university-adjacent informal physics learning contexts in Sweden
- 2022
-
Ingår i: Physical Review Physics Education Research. - : American Physical Society. - 2469-9896. ; 18:2
-
Tidskriftsartikel (refereegranskat)abstract
- For young women, inbound identity trajectories into physics are generally regarded as exceptional. In this study, we investigated the experiences that young women have which may support their sustained interest and achievement in physics, and their ongoing inbound trajectories into post-secondary physics education. To understand these experiences, we look to the role of informal physics learning (IPL) environments as spaces which can offer resources that support women's trajectories into physics. In this paper, we highlight the important role of what we call "university-adjacent" IPL experiences-internships, summer schools, and associations that connect secondary students with the research lives of physicists. Focusing on case studies of six women enrolled in post-secondary physics programs across Sweden, we identify the various forms of resources made available through IPL environments, and how these create possibilities for young women to engage in forms of identity work that contribute to the construction of new possible selves in physics. Findings suggest that young women can access important relational and ideational resources through university-adjacent IPL programs. Relational resources included (a) supportive social networks, (b) enduring relationships, and (c) relatability. Importantly, our research finds that IPL opportunities that emphasize relationship building can create immersive experiences which go beyond representation and rather emphasize opportunities to develop practice-linked identities. Ideational resources emerged as (a) sources of information which possibilized physics for participants, and (b) types of information that provided possibilities to learn about the life of a physicist. Finally, while we claim that IPL experiences provide important possibilities for young women to immerse themselves in the practices of physics, we also discuss that these kinds of experiences remain inaccessible to most students, and thus reproduce a certain elitism in the field.
|
|
| 28. |
- Gonsalves, Allison J., et al.
(författare)
-
Using story-based methodologies to explore physics identities : How do moments add up to a life in physics?
- 2023
-
Ingår i: Physical Review Physics Education Research. - : American Physical Society. - 2469-9896. ; 19:2
-
Tidskriftsartikel (refereegranskat)abstract
- This article details methodologies employed to enable sharing and coconstructing the stories of threewomen’s lives in physics. The first case explores the usefulness of timeline interviewing, where participantsnarrate episodes that are coconstructed with the researcher as meaningful over time. We illustrate thismethod in the case of a mature student in Sweden from a working-class background who shared momentsthat added up to a life outside of physics and then a sharp turn into physics later in life. The second caseexplores life-history interviewing using a narrative-inquiry approach and deep relationship building whichenabled the coconstruction of stories of experiences over time. These moments are coconstructed with theresearcher and analyzed using an intersectionality lens to yield a story depicting the transnationalexperiences of a woman of color moving across various European contexts into the North Americanphysics context. The final case is of a first-generation Canadian woman of color who shared her navigationsof in and out of school physics via a method known as the “Rivers of Life.” Using this method, theparticipant narrates their experiences with physics as a river, using metaphorical tools like rafts, rocks,rapids, tributaries to discuss various moments described as twists and turns over time that together amountto a life in physics. We discuss the value of different approaches to coconstructing narratives withparticipants and, in particular, the need for this kind of research in physics context
|
|
| 29. |
- Gustin, Klara, et al.
(författare)
-
Assessment of Joint Impact of Iodine, Selenium, and Zinc Status on Women's Third-Trimester Plasma Thyroid Hormone Concentrations
- 2022
-
Ingår i: Journal of Nutrition. - : Elsevier BV. - 1541-6100 .- 0022-3166. ; 152:7, s. 1737 -1746
-
Tidskriftsartikel (refereegranskat)abstract
- Background Iodine is essential for synthesizing thyroid hormones, but other micronutrients are also required for optimal thyroid function. However, there is a lack of data on combined micronutrient status in relation to thyroid hormones in pregnancy. Objectives We aimed to assess the joint associations of iodine, selenium, and zinc status with plasma concentrations of thyroid hormones and thyroid-stimulating hormone (TSH) in pregnancy. Methods We included 531 pregnant women (aged 22-40 y) participating in a Swedish birth cohort who provided blood and spot urine samples in gestational weeks 27-33 (mean: 29). Associations of urinary iodine concentration (UIC), plasma selenium concentration, and plasma zinc concentration (measured by inductively coupled plasma mass spectrometry) with plasma hormone concentrations [total and free thyroxine (tT4, fT4), total and free triiodothyronine (tT3, fT3), and TSH] were explored with Bayesian kernel machine regression (BKMR; n = 516; outliers excluded) and multivariable-adjusted linear regression (n = 531; splined for nonlinear associations). Results Median (IQR) micronutrient concentrations were 112 mu g/L (80-156 mu g/L) for UIC, 67 mu g/L (58-76 mu g/L) for plasma selenium, and 973 mu g/L (842-1127 mu g/L) for plasma zinc; the former 2 median values were below recommended concentrations (150 mu g/L and 70 mu g/L, respectively). Mean +/- SD TSH concentration was 1.7 +/- 0.87 mIU/L, with 98% < 4 mIU/L. BKMR showed a positive trend of joint micronutrient concentrations in relation to TSH. Plasma zinc was most influential for all hormones but tT3, for which plasma selenium was most influential. In adjusted linear regression models, zinc was positively associated with tT4, tT3, and TSH, and <1200 mu g/L also with fT4 and fT3. Selenium was inversely associated with fT3, and Conclusions Pregnant women's plasma TSH concentrations in the early third trimester increased with increasing joint status of iodine, selenium, and zinc. Zinc and selenium were more influential than iodine for the hormone concentrations. Multiple micronutrients need consideration in future studies of thyroid hormone status.
|
|
| 30. |
- Haider, Zahra, et al.
(författare)
-
DNA methylation and copy number variation profiling of T-cell lymphoblastic leukemia and lymphoma
- 2020
-
Ingår i: Blood Cancer Journal. - : Nature Publishing Group. - 2044-5385. ; 10:4
-
Tidskriftsartikel (refereegranskat)abstract
- Despite having common overlapping immunophenotypic and morphological features, T-cell lymphoblastic leukemia (T-ALL) and lymphoma (T-LBL) have distinct clinical manifestations, which may represent separate diseases. We investigated and compared the epigenetic and genetic landscape of adult and pediatric T-ALL (n = 77) and T-LBL (n = 15) patient samples by high-resolution genome-wide DNA methylation and Copy Number Variation (CNV) BeadChip arrays. DNA methylation profiling identified the presence of CpG island methylator phenotype (CIMP) subgroups within both pediatric and adult T-LBL and T-ALL. An epigenetic signature of 128 differentially methylated CpG sites was identified, that clustered T-LBL and T-ALL separately. The most significant differentially methylated gene loci included the SGCE/PEG10 shared promoter region, previously implicated in lymphoid malignancies. CNV analysis confirmed overlapping recurrent aberrations between T-ALL and T-LBL, including 9p21.3 (CDKN2A/CDKN2B) deletions. A significantly higher frequency of chromosome 13q14.2 deletions was identified in T-LBL samples (36% in T-LBL vs. 0% in T-ALL). This deletion, encompassing the RB1, MIR15A and MIR16-1 gene loci, has been reported as a recurrent deletion in B-cell malignancies. Our study reveals epigenetic and genetic markers that can distinguish between T-LBL and T-ALL, and deepen the understanding of the biology underlying the diverse disease localization.
|
|
| 31. |
|
|
| 32. |
- Hammar, Tora, 1984-, et al.
(författare)
-
Patients satisfied with e-prescribing in Sweden: a survey of a nationwide implementation
- 2011
-
Ingår i: Journal of pharmaceutical health services research. - : Oxford University Press (OUP). - 1759-8885. ; 2:2, s. 97-105
-
Tidskriftsartikel (refereegranskat)abstract
- ObjectiveTo evaluate Swedish patients’ attitudes towards e-prescribing, including the transfer of e-prescriptions, electronic storing of prescriptions and mail-order prescriptions.MethodsThis study was a nationwide survey of attitudes among Swedish patients and was conducted as a postal questionnaire. The questionnaire was developed for the purpose of thisstudy and aimed to evaluate respondents’ views concerning e-prescribing, electronic storingof e-prescriptions and mail-order prescriptions from aspects including safety, personal benefits and effectiveness. A study population of 1500 individuals meeting the inclusioncriteria was randomly selected from a database of individuals in Sweden storing prescriptions electronically (n = 5 840 599).The response rate was 52% (739/1429).Key findingsThe vast majority of the respondents had a positive attitude towards e-prescriptions (85%, 628/739) and electronic storing of prescriptions (86%, 633/739), andregarded e-prescriptions to be safe (79%, 584/739), creating benefits for them (78%, 576/739) and promoting faster dispensing (69%, 512/739). Significant differences in attitudes towards e-prescriptions and electronic storing of prescriptions were detected between age groups. Patients storing all their prescriptions electronically had a more positive attitudetowards both e-prescriptions and electronic storing of prescriptions compared to patientswho stated they had paper prescriptions. The most common suggestion (n = 27) for improvement was to extend the information given about the services.ConclusionOur nationwide survey showed that a vast majority of Swedish patients had positive attitudes towards e-prescriptions and electronic storing of prescriptions. However, a need for extended information regarding e-prescribing was identified.
|
|
| 33. |
- Hammar, Tora, et al.
(författare)
-
Swedish pharmacists value ePrescribing : a survey of a nation-wide implementation
- 2010
-
Ingår i: Journal of Pharmaceutical Health Services Research. - : Wiley-Blackwell. - 1759-8885. ; 1:1, s. 23-32
-
Tidskriftsartikel (refereegranskat)abstract
- ObjectiveTo evaluate Swedish pharmacists’ attitudes towards ePrescribing, including thetransfer of ePrescriptions, electronic storing of prescriptions and mail-order prescriptions.MethodThis study was conducted as a web-based survey among 500 randomly selectedSwedish community pharmacists. The questionnaire included open-ended questions,multiple-choice questions and statements to which respondents gave their degree ofagreement on a six-point Likert-type rating scale. Free-text answers were categorized intothe most commonly mentioned opinions. Differences in respondents’ general characteristicsand their level of satisfaction with ePrescribing were tested for significance using χ2test. The survey had a response rate of 52% (259/500). 96% (248/259) of the respondentswere female, and 76% (196/259) were aged 40–64 years.Key findings Swedish community pharmacists were generally satisfied with ePrescribing(98%, 253/259). No significant (P > 0.05) difference in the general satisfaction could beexplained by the respondents’ age, gender or years in practice. A majority of the respondentsregarded ePrescriptions and electronic storing of prescriptions as being safe for patients (95 and93% respectively), providing patient benefits (96 and 95% respectively), being cost-effectivefor the pharmacy (92 and 91% respectively) and contributing to better communication andrelationships with both patients and prescribers (62–88%). The positive aspects of ePrescribingmost frequently mentioned in free-text answers were being safe (72%, 187/259) and timesaving(55%, 143/259). However, several weaknesses with ePrescribing were also describedby the respondents, as well as suggestions for improvement.ConclusionOur nationwide survey of Swedish community pharmacists’ attitudestowards ePrescribing shows that pharmacists are generally satisfied with it, including thetransfer of ePrescriptions, electronic storing of prescriptions and to a lower degree mailorderprescriptions.
|
|
| 34. |
- Hammarström, Per, et al.
(författare)
-
A Fluorescent Pentameric Thiophene Derivative Detects in Vitro-Formed Prefibrillar Protein Aggregates
- 2010
-
Ingår i: BIOCHEMISTRY. - : ACS American Chemical Society. - 0006-2960 .- 1520-4995. ; 49:32, s. 6838-6845
-
Tidskriftsartikel (refereegranskat)abstract
- Protein aggregation is associated with a wide range of diseases, and molecular probes that are able to detect a diversity of misfolded protein assemblies are of great importance. The identification of prefibrillar states preceding the formation of well-defined amyloid fibrils is of particular interest both because of their likely role in the mechanism of fibril formation and because of the growing awareness that these species are likely to play a critical role in the pathogenesis of protein deposition diseases. Herein, we explore the use of an anionic oligothiophene derivative, p-FTAA, for detection of prefibrillar protein aggregates during in vitro fibrillation of three different amyloidogenic proteins (insulin, lysozyme, and prion protein). p-FTAA generally detected prefibrillar protein aggregates that could not be detected by thioflavine T fluorescence and in addition showed high fluorescence when bound to mature fibrils. Second, the kinetics of protein aggregation or the formation of amyloid fibrils of insulin was not extensively influenced by the presence of various concentrations of p-FTAA. These results establish the use of p-FTAA as an additional tool for studying the process of protein aggregation.
|
|
| 35. |
- Hammarström, Per, et al.
(författare)
-
Porcine prion protein amyloid
- 2015
-
Ingår i: Prion. - : Taylor andamp; Francis: STM, Behavioural Science and Public Health Titles. - 1933-6896 .- 1933-690X. ; 9:4, s. 266-277
-
Tidskriftsartikel (refereegranskat)abstract
- Mammalian prions are composed of misfolded aggregated prion protein (PrP) with amyloid-like features. Prions are zoonotic disease agents that infect a wide variety of mammalian species including humans. Mammals and by-products thereof which are frequently encountered in daily life are most important for human health. It is established that bovine prions (BSE) can infect humans while there is no such evidence for any other prion susceptible species in the human food chain (sheep, goat, elk, deer) and largely prion resistant species (pig) or susceptible and resistant pets (cat and dogs, respectively). PrPs from these species have been characterized using biochemistry, biophysics and neurobiology. Recently we studied PrPs from several mammals in vitro and found evidence for generic amyloidogenicity as well as cross-seeding fibril formation activity of all PrPs on the human PrP sequence regardless if the original species was resistant or susceptible to prion disease. Porcine PrP amyloidogenicity was among the studied. Experimentally inoculated pigs as well as transgenic mouse lines overexpressing porcine PrP have, in the past, been used to investigate the possibility of prion transmission in pigs. The pig is a species with extraordinarily wide use within human daily life with over a billion pigs harvested for human consumption each year. Here we discuss the possibility that the largely prion disease resistant pig can be a clinically silent carrier of replicating prions.
|
|
| 36. |
- Hammarström, Per, et al.
(författare)
-
Viruses and amyloids-a vicious liaison
- 2023
-
Ingår i: Prion. - : TAYLOR & FRANCIS INC. - 1933-6896 .- 1933-690X. ; 17:1, s. 82-104
-
Forskningsöversikt (refereegranskat)abstract
- The crosstalk between viral infections, amyloid formation and neurodegeneration has been discussed with varying intensity since the last century. Several viral proteins are known to be amyloidogenic. Post-acute sequalae (PAS) of viral infections is known for several viruses. SARS-CoV-2 and COVID-19 implicate connections between amyloid formation and severe outcomes in the acute infection, PAS and neurodegenerative diseases. Is the amyloid connection causation or just correlation? In this review we highlight several aspects where amyloids and viruses meet. The evolutionary driving forces that dictate protein amyloid formation propensity are different for viruses compared to prokaryotes and eukaryotes, while posttranslational endoproteolysis appears to be a common mechanism leading up to amyloid formation for both viral and human proteins. Not only do human and viral proteins form amyloid irrespective of each other but there are also several examples of co-operativity between amyloids, viruses and the inter-, and intra-host spread of the respective entity. Abnormal blood clotting in severe and long COVID and as a side effect in some vaccine recipients has been connected to amyloid formation of both the human fibrin and the viral Spike-protein. We conclude that there are many intersects between viruses and amyloids and, consequently, amyloid and virus research need to join forces here. We emphasize the need to accelerate development and implementation in clinical practice of antiviral drugs to preclude PAS and downstream neurological damage. There is also an ample need for retake on suitable antigen targets for the further development of next generation of vaccines against the current and coming pandemics.
|
|
| 37. |
- Hendry, Alexandra, et al.
(författare)
-
Atypical Development of Attentional Control Associates with Later Adaptive Functioning, Autism and ADHD Traits
- 2020
-
Ingår i: Journal of autism and developmental disorders. - : Springer Nature. - 0162-3257 .- 1573-3432. ; 50:11, s. 4085-4105
-
Tidskriftsartikel (refereegranskat)abstract
- Autism is frequently associated with difficulties with top-down attentional control, which impact on individuals’ mental health and quality of life. The developmental processes involved in these attentional difficulties are not well understood. Using a data-driven approach, 2 samples (N = 294 and 412) of infants at elevated and typical likelihood of autism were grouped according to profiles of parent report of attention at 10, 15 and 25 months. In contrast to the normative profile of increases in attentional control scores between infancy and toddlerhood, a minority (7–9%) showed plateauing attentional control scores between 10 and 25 months. Consistent with pre-registered hypotheses, plateaued growth of attentional control was associated with elevated autism and ADHD traits, and lower adaptive functioning at age 3 years.
|
|
| 38. |
- Herrmann, Uli S., et al.
(författare)
-
Structure-based drug design identifies polythiophenes as antiprion compounds
- 2015
-
Ingår i: Science Translational Medicine. - : AMER ASSOC ADVANCEMENT SCIENCE. - 1946-6234 .- 1946-6242. ; 7:299, s. 299ra123-
-
Tidskriftsartikel (refereegranskat)abstract
- Prions cause transmissible spongiform encephalopathies for which no treatment exists. Prions consist of PrPSc, a misfolded and aggregated form of the cellular prion protein (PrPC). We explore the antiprion properties of luminescent conjugated polythiophenes (LCPs) that bind and stabilize ordered protein aggregates. By administering a library of structurally diverse LCPs to the brains of prion-infected mice via osmotic minipumps, we found that antiprion activity required a minimum of five thiophene rings bearing regularly spaced carboxyl side groups. Solid-state nuclear magnetic resonance analyses and molecular dynamics simulations revealed that anionic side chains interacted with complementary, regularly spaced cationic amyloid residues of model prions. These findings allowed us to extract structural rules governing the interaction between LCPs and protein aggregates, which we then used to design a new set of LCPs with optimized binding. The new set of LCPs showed robust prophylactic and therapeutic potency in prion-infected mice, with the lead compound extending survival by greater than80% and showing activity against both mouse and hamster prions as well as efficacy upon intraperitoneal administration into mice. These results demonstrate the feasibility of targeted chemical design of compounds that may be useful for treating diseases of aberrant protein aggregation such as prion disease.
|
|
| 39. |
- Jackson, Carolyn, 1970-, et al.
(författare)
-
"Smart students get perfect scores in tests without studying much" : Why is an effortless achiever identity attractive, and for whom is it possible?
- 2015
-
Ingår i: Research Papers in Education. - : Informa UK Limited. - 0267-1522 .- 1470-1146. ; 30:4, s. 393-410
-
Tidskriftsartikel (refereegranskat)abstract
- Discourses about the value of effort and hard work are prevalent and powerful inmany western societies and educational contexts. Yet, paradoxically, in these samecontexts effortless achievement is often lauded, and in certain discourses is heraldedas the pinnacle of success and a sign of genius. In this paper we interrogatediscourses about effort and especially ‘effortlessness’ in Swedish and Englisheducational contexts. Informed, in particular, by interview data generated in uppersecondary schools in Sweden and secondary schools in England, we address thequestions: why is effortless achievement attractive, and for whom is it possible tobe discursively positioned as an effortless achiever? We argue that the subjectposition of ‘effortless achiever’ is not available to all categories of studentsequally, and for some it would be almost impossible to attain; the intersections ofgender, social class, ethnicity and institutional setting are influential. We end byconsidering the problematic implications of effortless achievement discourses.
|
|
| 40. |
- Jiang, R. C., et al.
(författare)
-
Increased CSF-decorin predicts brain pathological changes driven by Alzheimer's A beta amyloidosis
- 2022
-
Ingår i: Acta Neuropathologica Communications. - : Springer Science and Business Media LLC. - 2051-5960. ; 10:1
-
Tidskriftsartikel (refereegranskat)abstract
- Cerebrospinal fluid (CSF) biomarkers play an important role in diagnosing Alzheimer's disease (AD) which is characterized by amyloid-beta (A beta) amyloidosis. Here, we used two App knock-in mouse models, App(NL-F/NL-F) and App(NL-G-F/NL-G-F), exhibiting AD-like A beta pathology to analyze how the brain pathologies translate to CSF proteomes by label-free mass spectrometry (MS). This identified several extracellular matrix (ECM) proteins as significantly altered in App knock-in mice. Next, we compared mouse CSF proteomes with previously reported human CSF MS results acquired from patients across the AD spectrum. Intriguingly, the ECM protein decorin was similarly and significantly increased in both App(NL-F/NL-F) and App(NL-G-F/NL-G-F) mice, strikingly already at three months of age in the App(NL-F/NL-F) mice and preclinical AD subjects having abnormal CSF-A beta 42 but normal cognition. Notably, in this group of subjects, CSF-decorin levels positively correlated with CSF-A beta 42 levels indicating that the change in CSF-decorin is associated with early A beta amyloidosis. Importantly, receiver operating characteristic analysis revealed that CSF-decorin can predict a specific AD subtype having innate immune activation and potential choroid plexus dysfunction in the brain. Consistently, in App(NL-F/NL-F) mice, increased CSF-decorin correlated with both AP plaque load and with decorin levels in choroid plexus. In addition, a low concentration of human A beta 42 induces decorin secretion from mouse primary neurons. Interestingly, we finally identify decorin to activate neuronal autophagy through enhancing lysosomal function. Altogether, the increased CSF-decorin levels occurring at an early stage of A beta amyloidosis in the brain may reflect pathological changes in choroid plexus, present in a subtype of AD subjects.
|
|
| 41. |
|
|
| 42. |
|
|
| 43. |
- Johansson, Anders, 1987, et al.
(författare)
-
De oväntade naturvetarna: Vad kan vi lära av studenters olika vägar in i universitetsfysik?
- 2023
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Utbildningar inom fysik är i både svensk och internationell kontext bland de minst jämställda och med lägst mångfald både när det gäller naturvetenskapliga och ingenjörsprogram [1]. I det pågående VR-finansierade projektet “De oväntade naturvetarna” ställer vi frågan vad vi kan lära oss av studenter som gått mot strömmen och valt att läsa fysik. Projektet bygger på livsberättelseintervjuer med 21 fysikstudenter som på något sätt uppfattar sin egen bana till fysiken som icke-konventionell. Vi har undersökt vad som möjliggjort för dessa studenter att ta sig till universitetet, och specifikt en fysikutbildning. I presentationen sammanfattas projektet. Resultatet visar hur aktiviteter utanför skolan kan ha betydelse; informella men universitetsrelaterade aktiviteter som sommarskolor och forskarbesök, men också deltagande i naturvetenskapliga sammanhang online, kan spela stor roll för relations- och identitetsbyggande som möjliggör ett deltagande i fysiken och en väg till en universitetsutbildning [2], [3]. Pågående delstudier vänder på perspektivet och ställer frågorna: Vad möjliggörs för individen genom ett deltagande i fysik, och hur blir vissa val av studier och karriär möjliga och legitima medan andra omöjliggörs i relation till samhälleliga normer, kön, klass och etnicitet. För några av våra informanter har fysik och naturvetenskap varit central för att möjliggöra en starkare känsla av sammanhang, med världen och andra människor. Detta har dock inte erbjudits av skolundervisningen i fysik, utan handlat om andra upplevelser, och först med stöd av vuxenutbildning på folkhögskola och basår har fysiken kunnat ta en central plats i deras liv, vilket har inneburit ett brott från annars alienerande liv och karriärer. En central slutsats är att breddat deltagande på så vis inte behöver handla om att delta i formell utbildning, eller att följa förväntade karriärvägar, naturvetenskap kan vara starkt meningsfullt i människors liv i andra former Referenser [1] Universitets- och högskolerådet, “Antagningsstatistik,” 2022. (accessed Oct. 18, 2021). [2] A. J. Gonsalves, A. Johansson, A.-S. Nyström, and A. T. Danielsson, “Other spaces for young women’s identity work in physics: Resources accessed through university-adjacent informal physics learning contexts in Sweden,” Phys. Rev. Phys. Educ. Res. , vol. 18, no. 2, p. 020118, Sep. 2022, doi: 10/gqwsp2. [3] A. T. Danielsson, A. Johansson, A.-S. Nyström, and A. J. Gonsalves, “Young peoples’ online science practices as a gateway to higher education STEM,” Res Sci Educ , Jan. 2023, doi: 10/grvp8w.
|
|
| 44. |
|
|
| 45. |
- Johansson, Anders, 1987, et al.
(författare)
-
Following or defying expectations – the choice narratives of “unexpected” physics students
- 2022
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Higher education physics has long been a field with a disproportionately skewed representation in terms of gender, class, and ethnicity. Responding to this challenge, this study explores the trajectories into higher education physics, with a particular focus on “unexpected” physics students. Drawing on semi-structured timeline-guided interviews with 20 students enrolled in university physics programmes across Sweden, we analyze the students’ accounts of their trajectories into physics as “choice narratives” (Holmegaard, 2015) and as “narratives of location” (Anthias, 2005). We ask which choice narratives are used, and how these become (im)possible and legitimate in relation to narratives of location and wider societal discourses. In line with earlier research, many of our interviewees describe a fascination for science and for understanding the world, often described as established already in childhood. When growing up in a supporting academically oriented family, cultivating an interest in physics often becomes an obvious and easy path, and this is the case for many of the women in our sample growing up in middle-class families. For others, being given an opportunity to express a passion for science despite family and society not expecting it is an important transformative experience. Interviewees describe wanting to be challenged and recognized for their performance. Here, physics is seen as a difficult subject, bestowing prestige when mastered. Achieving this kind of recognition can be an expected attainment in middle-class families and striving migrant families, but also a way of proving oneself against all odds for those from a non-academic background. The choice of physics is also described by some as a possibility to contribute to one’s community. In earlier research, this has not been highlighted as a common motivation for choosing physics, but we find that this is narrated in relation to marginalized class and ethnic positions, and still uncommon among the women with middle-class background. However, some of the women frame the choice of studying physics as a contribution simply because it breaks expectations and may provide a role model for other underrepresented students. In contrast to the traditional picture of physics as a “pure”, “smart”, and “prestigious” field of study pursued by students interested in understanding how the world works, our results show that alternate ways of approaching physics studies are possible. However, these approaches are both limited and possibilized by the gendered, classed, and racialized locations of prospective students. An opportunity for reconceiving the role of physics for all students, both in and outside school, is given by considering these alternative approaches to the subject. Anthias, F. (2005). Social Stratification and Social Inequality: Models of Intersectionality and Identity. In F. Devine, M. Savage, J. Scott, & R. Crompton (Eds.), Rethinking class: culture, identities and lifestyles (pp. 24–45). Palgrave Macmillan. Holmegaard, H. T. (2015). Performing a choice-narrative: A qualitative study of the patterns in STEM students’ higher education choices. International Journal of Science Education , 37(9), 1454–1477. https://doi.org/10/gctkn7
|
|
| 46. |
|
|
| 47. |
- Johansson, Ann-Sofie, et al.
(författare)
-
Fish oil delays lymphoma progression in the TLL mouse
- 2010
-
Ingår i: Leukemia and Lymphoma. - : Informa UK Limited. - 1042-8194 .- 1029-2403. ; 51:11, s. 2092-2097
-
Tidskriftsartikel (refereegranskat)abstract
- The objective was to investigate the effects of omega-3 fatty acids, known for their anti-inflammatory effects, on time to lymphoma progression and survival in the TLL mouse, a strain genetically prone to developing aggressive T-cell lymphoma. Compared to mice fed a standard diet, TLL mice fed omega-3 (menhaden fish oil) experienced a significant delay in disease progression and were more likely to remain alive and symptom free during the first 8 months of the study. In contrast, omega-6 supplementation (corn oil) did not significantly affect lymphoma progression. Irrespective of diet, all mice eventually progressed, and 1-year survival was not different between the groups. Immunological analysis demonstrated a significantly altered B-cell compartment and fewer NK cells in healthy C57Black6 mice fed omega-3, compared to controls. In conclusion, a diet rich in omega-3 fatty acids delays lymphoma development in the TLL mouse possibly by mechanisms that include complex effects on immune function.
|
|
| 48. |
|
|
| 49. |
- Johansson, Ann-Sofie, 1967-, et al.
(författare)
-
Germ line insertions of moloney murine leukemia virus in the TLL mouse causes site-specific differences in lymphoma/leukemia frequency and tumor immunophenotype
- 2006
-
Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 26:4B, s. 2873-2878
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Moloney murine leukemia virus (Mo-MLV) has proven valuable for studies of the pathogenesis of malignant lymphoma. Inoculation of newborn mice induces T cell lymphoma with 100% incidence. The TLL (T cell lymphoma/leukemia)-strain was previously established and was shown to spontaneously develop T cell lymphoma at high frequency. Materials and Methods: Differential screening of cDNA libraries was performed to discover an involvement of Mo-MLV and genomic sequencing was used to identify the chromosomal position of Mo-MLV proviral integration sites. Immunophenotypes of the tumors were established by flow cytometry. Disease frequency curves were created according to the Kaplan-Meier method. Results: Two independent Mo-MLV germ line integrations were characterized on chromosomes 2 and 14, giving rise to two substrains of mice denoted TLL-2 and TLL-14. The chromosomal position of the integrated provirus affected the frequency of disease, as well as the immunophenotype of the tumors. Conclusion: The data suggest that factors influencing the transcriptional activity of the chromosomal regions, leading to differences in proviral expression, could underlie the observed difference in tumor frequency.
|
|
| 50. |
- Johansson, Lovisa, et al.
(författare)
-
Amyloid beta 1-40 and 1-42 fibril ratios and maturation level cause conformational differences with minimal impact on autophagy and cytotoxicity
- 2024
-
Ingår i: Journal of Neurochemistry. - : WILEY. - 0022-3042 .- 1471-4159.
-
Tidskriftsartikel (refereegranskat)abstract
- The amyloid beta (A beta) peptide has a central role in Alzheimer's disease (AD) pathology. The peptide length can vary between 37 and 49 amino acids, with A beta 1-42 being considered the most disease-related length. However, A beta 1-40 is also found in A beta plaques and has shown to form intertwined fibrils with A beta 1-42. The peptides have previously also shown to form different fibril conformations, proposed to be related to disease phenotype. To conduct more representative in vitro experiments, it is vital to uncover the impact of different fibril conformations on neurons. Hence, we fibrillized different A beta 1-40:42 ratios in concentrations of 100:0, 90:10, 75:25, 50:50, 25:75, 10:90 and 0:100 for either 24 h (early fibrils) or 7 days (aged fibrils). These were then characterized based on fibril width, LCO-staining and antibody-staining. We further challenged differentiated neuronal-like SH-SY5Y human cells with the different fibrils and measured A beta content, cytotoxicity and autophagy function at three different time-points: 3, 24, and 72 h. Our results revealed that both A beta 1-40:42 ratio and fibril maturation affect conformation of fibrils. We further show the impact of these conformation changes on the affinity to commonly used A beta antibodies, primarily affecting A beta 1-40 rich aggregates. In addition, we demonstrate uptake of the aggregates by neuronally differentiated human cells, where aggregates with higher A beta 1-42 ratios generally caused higher cellular levels of A beta. These differences in A beta abundance did not cause changes in cytotoxicity nor in autophagy activation. Our results show the importance to consider conformational differences of A beta fibrils, as this can have fundamental impact on A beta antibody detection. Overall, these insights underline the need for further exploration of the impact of conformationally different fibrils and the need to reliably produce disease relevant A beta aggregates.image
|
|
