| 1. |
- Andersson, Annika, et al.
(författare)
-
Membrane integration and topology of RIFIN and STEVOR proteins of the Plasmodium falciparum parasite
- 2020
-
Ingår i: The FEBS Journal. - : Wiley. - 1742-464X .- 1742-4658. ; 287:13, s. 2744-2762
-
Tidskriftsartikel (refereegranskat)abstract
- The malarial parasite Plasmodium exports its own proteins to the cell surfaces of red blood cells (RBCs) during infection. Examples of exported proteins include members of the repetitive interspersed family (RIFIN) and subtelomeric variable open reading frame (STEVOR) family of proteins from Plasmodium falciparum. The presence of these parasite-derived proteins on surfaces of infected RBCs triggers the adhesion of infected cells to uninfected cells (rosetting) and to the vascular endothelium potentially obstructing blood flow. While there is a fair amount of information on the localization of these proteins on the cell surfaces of RBCs, less is known about how they can be exported to the membrane and the topologies they can adopt during the process. The first step of export is plausibly the cotranslational insertion of proteins into the endoplasmic reticulum (ER) of the parasite, and here, we investigate the insertion of three RIFIN and two STEVOR proteins into the ER membrane. We employ a well-established experimental system that uses N-linked glycosylation of sites within the protein as a measure to assess the extent of membrane insertion and the topology it assumes when inserted into the ER membrane. Our results indicate that for all the proteins tested, transmembranes (TMs) 1 and 3 integrate into the membrane, so that the protein assumes an overall topology of Ncyt-Ccyt. We also show that the segment predicted to be TM2 for each of the proteins likely does not reside in the membrane, but is translocated to the lumen.
|
|
| 2. |
- Reddy, Sreenivasulu B., et al.
(författare)
-
Direct contact between Plasmodium falciparum and human B-cells in a novel co-culture increases parasite growth and affects B-cell growth
- 2021
-
Ingår i: Malaria Journal. - : Springer Science and Business Media LLC. - 1475-2875. ; 20:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Plasmodium falciparum parasites cause malaria and co-exist in humans together with B-cells for long periods of time. Immunity is only achieved after repeated exposure. There has been a lack of methods to mimic the in vivo co-occurrence, where cells and parasites can be grown together for many days, and it has been difficult with long time in vitro studies. Methods and results: A new method for growing P. falciparum in 5% CO2 with a specially formulated culture medium is described. This knowledge was used to establish the co-culture of live P. falciparum together with human B-cells in vitro for 10 days. The presence of B-cells clearly enhanced parasite growth, but less so when Transwell inserts were used (not allowing passage of cells or merozoites), showing that direct contact is advantageous. B-cells also proliferated more in presence of parasites. Symbiotic parasitic growth was verified using CESS cell-line and it showed similar results, indicating that B-cells are indeed the cells responsible for the effect. In malaria endemic areas, people often have increased levels of atypical memory B-cells in the blood, and in this assay it was demonstrated that when parasites were present there was an increase in the proportion of CD19 + CD20 + CD27 − FCRL4 + B-cells, and a contraction of classical memory B-cells. This effect was most clearly seen when direct contact between B-cells and parasites was allowed. Conclusions: These results demonstrate that P. falciparum and B-cells undoubtedly can affect each other when allowed to multiply together, which is valuable information for future vaccine studies.
|
|
| 3. |
- Stea, T. H., et al.
(författare)
-
Mapping the Concept, Content, and Outcome of Family-Based Outdoor Therapy for Children and Adolescents with Mental Health Problems : A Scoping Review
- 2022
-
Ingår i: International Journal of Environmental Research and Public Health. - : MDPI AG. - 1661-7827 .- 1660-4601. ; 19:10
-
Forskningsöversikt (refereegranskat)abstract
- Outdoor therapy and family-based therapy are suggested to be promising interventions for the treatment of mental health problems. The aim of the present scoping review was to systematically map the concept, content, and outcome of combining family-and outdoor-based therapy for children and adolescents with mental health problems. The Joanna Briggs Institute methodology and PRISMA guidelines were applied. Eligible qualitative and quantitative studies were screened, included, and extracted for data. Seven studies were included. Findings from these studies indicated that family-based outdoor therapy programs have a positive impact on family-and peer relationships, adolescent behavior, mental health, self-perceptions (self-concept), school success, social engagement, and delinquency rates. However, participant characteristics, study design, and content and mode of delivery of the interventions varied substantially, hence preventing detailed comparison of outcomes across studies. In addition, most of the studies included few participants and lacked population diversity and comparable control groups. Although important ethical concerns were raised, such as non-voluntary participation in some of the programs, there was a lack of reporting on safety. This review indicates that a combination of family-and outdoor-based therapy may benefit mental health among children and adolescents, but due to the limited number of studies eligible for inclusion and high levels of heterogeneity, it was difficult to draw firm conclusions. Thus, future theory-based studies using robust designs are warranted.
|
|
| 4. |
- Västberg, Amanda, et al.
(författare)
-
Investigating thermally induced aggregation of Somatropin- new insights using orthogonal techniques
- 2023
-
Ingår i: International Journal of Pharmaceutics. - : Elsevier B.V.. - 0378-5173 .- 1873-3476. ; 637
-
Tidskriftsartikel (refereegranskat)abstract
- Three orthogonal techniques were used to provide new insights into thermally induced aggregation of the therapeutic protein Somatropin at pH 5.8 and 7.0. The techniques were Dynamic Light Scattering (DLS), Asymmetric Flow-Field Flow-Fractionation (AF4), and the TEM-based analysis system MiniTEM™. In addition, Differential Scanning Calorimetry (DSC) was used to study the thermal unfolding and stability. DSC and DLS were used to explain the initial aggregation process and aggregation rate at the two pH values. The results suggest that less electrostatic stabilization seems to be the main reason for the faster initial aggregation at pH 5.8, i.e., closer to the isoelectric point of Somatropin. AF4 and MiniTEM were used to investigate the aggregation pathway further. Combining the results allowed us to demonstrate Somatropin's thermal aggregation pathway at pH 7.0. The growth of the aggregates appears to follow two steps. Smaller elongated aggregates are formed in the first step, possibly initiated by partly unfolded species. In the second step, occurring during longer heating, the smaller aggregates assemble into larger aggregates with more complex structures. © 2023 The Author(s)
|
|
