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- Centlow, Magnus
(author)
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Gene and Protein Profiling of the Preeclamptic Placenta
- 2008
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Doctoral thesis (other academic/artistic)abstract
- Aims State-of-the-art methodology was used to screen and profile the placenta, gene and protein expression, for changes related to preeclampsia (PE) and cases with increased resistance in the uterine arteries. Women with increased resistance in the uterine arteries have increased risk of developing PE. Since not all of them develop PE, this group, identified by Doppler ultrasound, was included to search for genes and/or proteins that may protect them from developing PE. Results The PE placenta showed increased gene expression of fetal hemoglobin (Hb). Protein expression analysis confirmed the accumulation of free Hb, particularly the gamma chain was detected in the vascular lumen. Patients with increased resistance in the uterine arteries, expressed as a notch in blood velocity tracings recorded with Doppler ultrasound. Notching without PE, showed increased expression of genes related to apoptosis and antigen presentation in their placentas. In the notch placentas that later developed PE, an increased expression of genes related to inflammatory cell movement was seen. Antibody microarray screening of maternal plasma showed that late and early onset PE as well as PE with notching and IUGR showed different inflammatory responses. Conclusions The changes in gene expression suggested that PE may be a three-stage disease with notch as a reversible middle stage. Accumulation of inflammatory cells in the notch placenta may cause inflammation that drives the pathophysiology into PE. Increased expression of antigen presenting genes may protect the notch placenta from pro-inflammatory damage thereby preventing progression into PE. Free fetal Hb was identified as a possible placental factor that further induces inflammation and tissue damage. Increased maternal plasma levels of free fetal Hb may be used as a prognostic and diagnostic marker for PE. The maternal immune reaction and inflammatory response may be important factors that further determine the severity and the clinical manifestations of PE.
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| 3. |
- Eriksson, Nicolina, et al.
(author)
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The action research story of a student–teacher : Change is not easy and it takes time, effort, and critical reflection
- 2017
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In: International Journal of Action Research. - : Rainer Hampp Verlag. - 1861-1303 .- 1861-9916. ; 13:1, s. 51-74
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Journal article (peer-reviewed)abstract
- The purpose of this paper is to report on the pedagogical and research learning I experienced as a physical education student–teacher engaged in an action research project, for which I designed and implemented an innovative teaching model. In my roles as student–teacher and researcher, I wanted to examine the impact of using Sport Education in a Finnish school context by analysing and understanding my teaching as well as my students’ experiences. Data collection included my personal reflective journal, video observations, student group interviews, and student diaries. The results of this study reinforced previously reported benefits of Sport Education, although there are contextual and pragmatic issues that need to be acknowledged. Even though implementing a new pedagogical approach was time-consuming, stressful, and full of real-world challenges as well as the additional demands of the action research project, I still learned a great deal about teaching and research.
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| 4. |
- Fagerberg, Eric, et al.
(author)
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Self-Diffusive Properties of the Intrinsically Disordered Protein Histatin 5 and the Impact of Crowding Thereon : A Combined Neutron Spectroscopy and Molecular Dynamics Simulation Study
- 2021
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In: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-6106 .- 1520-5207.
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Journal article (peer-reviewed)abstract
- Intrinsically disordered proteins (IDPs) are proteins that, in comparison with globular/structured proteins, lack a distinct tertiary structure. Here, we use the model IDP, Histatin 5, for studying its dynamical properties under self-crowding conditions with quasi-elastic neutron scattering in combination with full atomistic molecular dynamics (MD) simulations. The aim is to determine the effects of crowding on the center-of-mass diffusion as well as the internal diffusive behavior. The diffusion was found to decrease significantly, which we hypothesize can be attributed to some degree of aggregation at higher protein concentrations, (≥100 mg/mL), as indicated by recent small-angle X-ray scattering studies. Temperature effects are also considered and found to, largely, follow Stokes-Einstein behavior. Simple geometric considerations fail to accurately predict the rates of diffusion, while simulations show semiquantitative agreement with experiments, dependent on assumptions of the ratio between translational and rotational diffusion. A scaling law that previously was found to successfully describe the behavior of globular proteins was found to be inadequate for the IDP, Histatin 5. Analysis of the MD simulations show that the width of the distribution with respect to diffusion is not a simplistic mirroring of the distribution of radius of gyration, hence, displaying the particular features of IDPs that need to be accounted for.
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| 6. |
- Naumann, Marcel, et al.
(author)
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Phenotypes and malignancy risk of different FUS mutations in genetic amyotrophic lateral sclerosis
- 2019
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In: Annals of Clinical and Translational Neurology. - : John Wiley & Sons. - 2328-9503. ; 6:12, s. 2384-2394
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Journal article (peer-reviewed)abstract
- Objective: Mutations in Fused in Sarcoma (FUS or TLS) are the fourth most prevalent in Western European familial amyotrophic lateral sclerosis (ALS) populations and have been associated with causing both early and very late disease onset. FUS aggregation, DNA repair deficiency, and genomic instability are contributors to the pathophysiology of FUS-ALS, but their clinical significance per se and their influence on the clinical variability have yet to be sufficiently investigated. The aim of this study was to analyze genotype-phenotype correlations and malignancy rates in a newly compiled FUS-ALS cohort.Methods: We cross-sectionally reviewed FUS-ALS patient histories in a multicenter cohort with 36 novel cases and did a meta-analysis of published FUS-ALS cases reporting the largest genotype-phenotype correlation of FUS-ALS.Results: The age of onset (median 39 years, range 11-80) was positively correlated with the disease duration. C-terminal domain mutations were found in 90%. Among all, P525L and truncating/ frameshift mutations most frequently caused juvenile onset, rapid disease progression, and atypical ALS often associated with negative family history while the R521 mutation site was associated with late disease onset and pure spinal phenotype. Malignancies were found in one of 40 patients.Interpretation: We report the largest genotype-phenotype correlation of FUS-ALS, which enables a careful prediction of the clinical course in newly diagnosed patients. In this cohort, FUS-ALS patients did not have an increased risk for malignant diseases.
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