| 1. |
- Åberg, Anna, et al.
(författare)
-
Helicobacter pylori adapts to chronic infection and gastric disease via ph-responsive baba-mediated adherence
- 2017
-
Ingår i: Cell Host and Microbe. - : Elsevier BV. - 1931-3128 .- 1934-6069. ; 21:3, s. 376-389
-
Tidskriftsartikel (refereegranskat)abstract
- The BabA adhesin mediates high-affinity binding of Helicobacter pylori to the ABO blood group antigen-glycosylated gastric mucosa. Here we show that BabA is acid responsive-binding is reduced at low pH and restored by acid neutralization. Acid responsiveness differs among strains; often correlates with different intragastric regions and evolves during chronic infection and disease progression; and depends on pH sensor sequences in BabA and on pH reversible formation of high-affinity binding BabA multimers. We propose that BabA's extraordinary reversible acid responsiveness enables tight mucosal bacterial adherence while also allowing an effective escape from epithelial cells and mucus that are shed into the acidic bactericidal lumen and that bio-selection and changes in BabA binding properties through mutation and recombination with babA-related genes are selected by differences among individuals and by changes in gastric acidity over time. These processes generate diverse H. pylori subpopulations, in which BabA's adaptive evolution contributes to H. pylori persistence and overt gastric disease.
|
|
| 2. |
- Brännström, Kristoffer, et al.
(författare)
-
Scanning electron microscopy as a tool for evaluating morphology of amyloid structures formed on surface plasmon resonance chips
- 2018
-
Ingår i: Data in Brief. - : Elsevier. - 2352-3409. ; 19, s. 1166-1170
-
Tidskriftsartikel (refereegranskat)abstract
- We demonstrate the use of Scanning Electron microscopy (SEM) in combination with Surface Plasmon Resonance (SPR) to probe and verify the formation of amyloid and its morphology on an SPR chip. SPR is a technique that measures changes in the immobilized weight on the chip surface and is frequently used to probe the formation and biophysical properties of amyloid structures. In this context it is of interest to also monitor the morphology of the formed structures. The SPR chip surface is made of a layer of gold, which represent a suitable material for direct analysis of the surface using SEM. The standard SPR chip used here (CM5-chip, GE Healthcare, Uppsala, Sweden) can easily be disassembled and directly analyzed by SEM. In order to verify the formation of amyloid fibrils in our experimental conditions we analyzed also in-solution produced structures by using Transmission Electron Microscopy (TEM). For further details and experimental findings, please refer to the article published in Journal of Molecular Biology, (Brännström K. et al., 2018) [1].
|
|
| 3. |
- Brännström, Kristoffer, et al.
(författare)
-
The Properties of Amyloid-β Fibrils Are Determined by their Path of Formation
- 2018
-
Ingår i: Journal of Molecular Biology. - : Elsevier. - 0022-2836 .- 1089-8638. ; 430:13, s. 1940-1949
-
Tidskriftsartikel (refereegranskat)abstract
- Fibril formation of the amyloid-β peptide (Aβ) follows a nucleation-dependent polymerization process and is associated with Alzheimer's disease. Several different lengths of Aβ are observed in vivo, but Aβ1-40 and Aβ1-42 are the dominant forms. The fibril architectures of Aβ1-40 and Aβ1-42 differ and Aβ1-42 assemblies are generally considered more pathogenic. We show here that monomeric Aβ1-42 can be cross-templated and incorporated into the ends of Aβ1-40 fibrils, while incorporation of Aβ1-40 monomers into Aβ1-42 fibrils is very poor. We also show that via cross-templating incorporated Aβ monomers acquire the properties of the parental fibrils. The suppressed ability of Aβ1-40 to incorporate into the ends of Aβ1-42 fibrils and the capacity of Aβ1-42 monomers to adopt the properties of Aβ1-40 fibrils may thus represent two mechanisms reducing the total load of fibrils having the intrinsic, and possibly pathogenic, features of Aβ1-42 fibrils in vivo. We also show that the transfer of fibrillar properties is restricted to fibril-end templating and does not apply to cross-nucleation via the recently described path of surface-catalyzed secondary nucleation, which instead generates similar structures to those acquired via de novo primary nucleation in the absence of catalyzing seeds. Taken together these results uncover an intrinsic barrier that prevents Aβ1-40 from adopting the fibrillar properties of Aβ1-42 and exposes that the transfer of properties between amyloid-β fibrils are determined by their path of formation.
|
|
| 4. |
- Hrastinski, Stefan, 1980-, et al.
(författare)
-
Critical Imaginaries and Reflections on Artificial Intelligence and Robots in Postdigital K-12 Education
- 2019
-
Ingår i: Postdigital Science and Education. - : Springer Science and Business Media LLC. - 2524-485X .- 2524-4868 .- 2662-5326. ; 1:2, s. 427-445
-
Tidskriftsartikel (refereegranskat)abstract
- It is commonly suggested that emerging technologies will revolutionize education. In this paper, two such emerging technologies, artificial intelligence (AI) and educational robots (ER), are in focus. The aim of the paper is to explore how teachers, researchers and pedagogical developers critically imagine and reflect upon how AI and robots could be used in education. The empirical data were collected from discussion groups that were part of a symposium. For both AI and ERs, the need for more knowledge about these technologies, how they could preferably be used, and how the emergence of these technologies might affect the role of the teacher and the relationship between teachers and students, were outlined. Many participants saw more potential to use AI for individualization as compared with ERs. However, there were also more concerns, such as ethical issues and economic interests, when discussing AI. While the researchers/developers to a greater extent imagined ideal future technology-rich educational practices, the practitioners were more focused on imaginaries grounded in current practice.
|
|
| 5. |
- Iakovleva, Irina, et al.
(författare)
-
Enthalpic Forces Correlate with Selectivity of Transthyretin-Stabilizing Ligands in Human Plasma
- 2015
-
Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 58:16, s. 6507-6515
-
Tidskriftsartikel (refereegranskat)abstract
- The plasma protein transthyretin (TTR) is linked to human amyloidosis. Dissociation of its native tetrameric assembly is a rate-limiting step in the conversion from a native structure into a pathological amyloidogenic fold. Binding of small molecule ligands within the thyroxine binding site of TTR can stabilize the tetrameric integrity and is a potential therapeutic approach. However, through the characterization of nine different tetramer-stabilizing ligands we found that unspecific binding to plasma components might significantly compromise ligand efficacy. Surprisingly the binding strength between a particular ligand and TTR does not correlate well with its selectivity in plasma. However, through analysis of the thermodynamic signature using isothermal titration calorimetry we discovered a better correlation between selectivity and the enthalpic component of the interaction. This is of specific interest in the quest for more efficient TTR stabilizers, but a high selectivity is an almost universally desired feature within drug design and the finding might have wide-ranging implications for drug design.
|
|
| 6. |
- Islam, Tohidul, et al.
(författare)
-
Morphological analysis of Apolipoprotein E binding to A beta Amyloid using a combination of Surface Plasmon Resonance, Immunogold Labeling and Scanning Electron Microscopy
- 2019
-
Ingår i: BMC Biotechnology. - : BMC. - 1472-6750. ; 19:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Immunogold labeling in combination with transmission electron microscopy analysis is a technique frequently used to correlate high-resolution morphology studies with detailed information regarding localization of specific antigens. Although powerful, the methodology has limitations and it is frequently difficult to acquire a stringent system where unspecific low-affinity interactions are removed prior to analysis.Results: We here describe a combinatorial strategy where surface plasmon resonance and immunogold labeling are used followed by a direct analysis of the sensor-chip surface by scanning electron microscopy. Using this approach, we have probed the interaction between amyloid-beta fibrils, associated to Alzheimer's disease, and apolipoprotein E, a well-known ligand frequently found co-deposited to the fibrillar form of A beta in vivo. The results display a lateral binding of ApoE along the amyloid fibrils and illustrates how the gold-beads represent a good reporter of the binding.Conclusions: This approach exposes a technique with generic features which enables both a quantitative and a morphological evaluation of a ligand-receptor based system. The methodology mediates an advantage compared to traditional immunogold labeling since all washing steps can be monitored and where a high stringency can be maintained throughout the experiment.
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
- Willermark, Sara, 1988-
(författare)
-
Digital Didaktisk Design : Att utveckla undervisning i och för en digitaliserad skola
- 2018
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- I denna avhandling undersöks grundskollärares arbete med att utveckla sin undervisningspraktik med digital teknik. Mer precist undersöks hur en sådan utveckling kan identifieras, förstås och stödjas. Empirin härstammar primärt från ett treårigt aktionsorienterat skolutvecklingsprojekt i nordisk grundskola. Inom projektet samarbetade lärare från Sverige, Norge och Danmark för att utveckla nya undervisningsaktiviteter över nationsgränserna med stöd av digital teknik. Lärare organiserades inom olika ämnesspecifika designteam för att planera, implementera och utvärdera undervisningsaktiviteter, så kallad digital didaktisk design, vilket avser utformandet av en undervisningssekvens, som adresserar ett specifikt ämne inom ett visst ämnesområde. Det empiriska underlaget utgörs av dokumentation över den digitala didaktiska designen, deltagande observationer, intervjuer och innehållsanalyser samt en enkätundersökning. Två teoretiska ramverk används, TPACK (akronym för Technological Pedagogical And Content Knowledge) och verksamhetsteori. Resultaten påvisar en utveckling av lärares undervisningspraktik. Med stöd av digital teknik skapar lärare digital didaktisk design över nationsgränser, som ger upphov till nya aktiviteter, situationer och möten. Det krävdes dock både omfattande arbetsinsatser och ett praktiskt experimenterande under lång tid, för att lärarna skulle kunna utveckla digital didaktisk design som upplevdes meningsfull i den nya kontexten. Motsättningar och organisatoriska gränser mellan de samverkande lärarna identifierades som avgörande för utvecklingen, genom att ge upphov till förhandlingar, kompromisser och reflektion. Avhandlingen bidrar med ett verktyg för att identifiera och stödja lärares arbetemed att utveckla sin undervisningspraktik med digital teknik. Vidare föreslås en strategi för att identifiera och analysera lärares utveckling över tid. Avhandlingen bidrar också med kunskap om hur olika typer av spänningar och gränser vid samarbete kan stimulera till lärande för en digitaliserad undervisningspraktik, liksom rekommendationer för hur utbildningsinsatser för lärare kan utformas i syfte att stödja lärares utveckling av undervisningspraktiken.
|
|
