| 1. |
- Hermansson, A, et al.
(författare)
-
Inhibition of T cell response to native low-density lipoprotein reduces atherosclerosis
- 2010
-
Ingår i: The Journal of experimental medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 207:5, s. 1081-1093
-
Tidskriftsartikel (refereegranskat)abstract
- Immune responses to oxidized low-density lipoprotein (oxLDL) are proposed to be important in atherosclerosis. To identify the mechanisms of recognition that govern T cell responses to LDL particles, we generated T cell hybridomas from human ApoB100 transgenic (huB100tg) mice that were immunized with human oxLDL. Surprisingly, none of the hybridomas responded to oxidized LDL, only to native LDL and the purified LDL apolipoprotein ApoB100. However, sera from immunized mice contained IgG antibodies to oxLDL, suggesting that T cell responses to native ApoB100 help B cells making antibodies to oxLDL. ApoB100 responding CD4+ T cell hybridomas were MHC class II–restricted and expressed a single T cell receptor (TCR) variable (V) β chain, TRBV31, with different Vα chains. Immunization of huB100tgxLdlr−/− mice with a TRBV31-derived peptide induced anti-TRBV31 antibodies that blocked T cell recognition of ApoB100. This treatment significantly reduced atherosclerosis by 65%, with a concomitant reduction of macrophage infiltration and MHC class II expression in lesions. In conclusion, CD4+ T cells recognize epitopes on native ApoB100 protein, this response is associated with a limited set of clonotypic TCRs, and blocking TCR-dependent antigen recognition by these T cells protects against atherosclerosis.
|
|
| 2. |
|
|
| 3. |
- Hansson, Anneli, 1958-
(författare)
-
Arbete med skolutveckling - En potentiell gränszon mellan verksamheter? : Ett verksamhetsteoretiskt perspektiv på en svensk skolas arbete över tid med att verksamhetsintegrera IT
- 2013
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- I en skola som historiskt präglats av en differentierad arbetsorganisation och autonoma traditioner kan ett skolövergripande arbete med att verksamhetsintegrera informationsteknik antas ställa aktörerna inför en rad utmaningar som involverar både omskapande och nyskapande processer. Föreliggande studie utgör ett bidrag till att med en holistisk och verksamhetsteoretisk ansats utforska arbete med förändring, i detta fall ett arbete med att verksamhetsintegrera modern teknik, i skärningspunkten mellan en skolas arbete med att sprida och utveckla teknikbruk över skolan samt dess lärares arbete med pedagogisk praxisförändring. Studiens övergripande fråga löd: Hur kan arbete med skolutveckling förstås och förklaras i det potentiella spänningsfältet mellan arbete med skolförändring och lärares arbete med eller motstånd mot pedagogisk praxisförändring? Syftet var att utforska den förändringsprocess som uppstod när en skola satte i sikte att utveckla ”digitala” kompetenser och IT-stödd undervisning inom dess verksamhetsområde liksom att över tid följa lärare, IT-pedagoger och skolledare i detta arbete. Studien genomfördes över tre år mellan hösten 2008 och våren 2011 som en etnografiskt orienterad fallstudie vid en 7–9 skola i en mellanstor svensk stad. Dataproduktionen skedde genom närvaro vid skolan och på nätet genom deltagande och ickedeltagande observationer, genom informella samtal, semistrukturerade intervjuer, dokumentinsamling samt genom en enkät. Resultatet visar framför allt hur verksamhetsintegreringen av IT, bland de lärare som utforskar informationstekniken, i hög utsträckning motiveras av undervisningsrelaterade och elevutvecklande behov, medan arbetet med att leda skolans arbete med verksamhetsintegrering av IT i högre utsträckning motiveras av organisationsrelaterade behov, samt att dessa skilda motiv framträder på olika och systemiskt inkonsekvent sätt inom skolan. Utifrån studiens resultat formuleras tre interrelaterade utmaningar för skolutveckling. Dessa rör (a) praxis- och objektsförståelse, vilket uppfattas ha betydelse för möjligheter att åstadkomma gemensam riktning i ett kollektivt och flerstämmigt arbete, samt (b) förutsättningar för gränsöverskridande lärprocesser inom skolan mellan lärare sinsemellan liksom mellan lärare och skolledning jämte (c) processledarskap och dess förutsättningar.
|
|
| 4. |
- Hansson, EM, et al.
(författare)
-
Control of Notch-ligand endocytosis by ligand-receptor interaction
- 2010
-
Ingår i: Journal of cell science. - : The Company of Biologists. - 1477-9137 .- 0021-9533. ; 123:17Pt 17, s. 2931-2942
-
Tidskriftsartikel (refereegranskat)abstract
- In Notch signaling, cell-bound ligands activate Notch receptors on juxtaposed cells, but the relationship between ligand endocytosis, ubiquitylation and ligand-receptor interaction remains poorly understood. To study the specific role of ligand-receptor interaction, we identified a missense mutant of the Notch ligand Jagged1 (Nodder, Ndr) that failed to interact with Notch receptors, but retained a cellular distribution that was similar to wild-type Jagged1 (Jagged1WT) in the absence of active Notch signaling. Both Jagged1WT and Jagged1Ndr interacted with the E3 ubiquitin ligase Mind bomb, but only Jagged1WT showed enhanced ubiquitylation after co-culture with cells expressing Notch receptor. Cells expressing Jagged1WT, but not Jagged1Ndr, trans-endocytosed the Notch extracellular domain (NECD) into the ligand-expressing cell, and NECD colocalized with Jagged1WT in early endosomes, multivesicular bodies and lysosomes, suggesting that NECD is routed through the endocytic degradation pathway. When coexpressed in the same cell, Jagged1Ndr did not exert a dominant-negative effect over Jagged1WT in terms of receptor activation. Finally, in Jag1Ndr/Ndr mice, the ligand was largely accumulated at the cell surface, indicating that engagement of the Notch receptor is important for ligand internalization in vivo. In conclusion, the interaction-dead Jagged1Ndr ligand provides new insights into the specific role of receptor-ligand interaction in the intracellular trafficking of Notch ligands.
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
- Marklund, U, et al.
(författare)
-
Domain-specific control of neurogenesis achieved through patterned regulation of Notch ligand expression
- 2010
-
Ingår i: Development (Cambridge, England). - : The Company of Biologists. - 1477-9129 .- 0950-1991. ; 137:3, s. 437-445
-
Tidskriftsartikel (refereegranskat)abstract
- Homeodomain (HD) transcription factors and components of the Notch pathway [Delta1 (Dll1), Jagged1 (Jag1) and the Fringe (Fng) proteins] are expressed in distinct progenitor domains along the dorsoventral (DV) axis of the developing spinal cord. However, the internal relationship between these two regulatory pathways has not been established. In this report we show that HD proteins act upstream of Notch signalling. Thus, HD proteins control the spatial distribution of Notch ligands and Fng proteins, whereas perturbation of the Notch pathway does not affect the regional expression of HD proteins. Loss of Dll1 or Jag1 leads to a domain-specific increase of neuronal differentiation but does not affect the establishment of progenitor domain boundaries. Moreover, gain-of-function experiments indicate that the ability of Dll1 and Jag1 to activate Notch is limited to progenitors endogenously expressing the respective ligand. Fng proteins enhance Dll1-activated Notch signalling and block Notch activation mediated by Jag1. This finding, combined with the overlapping expression of Fng with Dll1 but not with Jag1, is likely to explain the domain-specific activity of the Notch ligands. This outcome is opposite to the local regulation of Notch activity in most other systems, including the Drosophila wing, where Fng co-localizes with Jagged/Serrate rather than Dll/Delta, which facilitates Notch signalling at regional boundaries instead of within domains. The regulation of Notch activation in the spinal cord therefore appears to endow specific progenitor populations with a domain-wide autonomy in the control of neurogenesis and prevents any inadequate activation of Notch across progenitor domain boundaries.
|
|
| 8. |
|
|
| 9. |
- Rodin, S, et al.
(författare)
-
Clonal culturing of human embryonic stem cells on laminin-521/E-cadherin matrix in defined and xeno-free environment
- 2014
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 5, s. 3195-
-
Tidskriftsartikel (refereegranskat)abstract
- Lack of robust methods for establishment and expansion of pluripotent human embryonic stem (hES) cells still hampers development of cell therapy. Laminins (LN) are a family of highly cell-type specific basement membrane proteins important for cell adhesion, differentiation, migration and phenotype stability. Here we produce and isolate a human recombinant LN-521 isoform and develop a cell culture matrix containing LN-521 and E-cadherin, which both localize to stem cell niches in vivo. This matrix allows clonal derivation, clonal survival and long-term self-renewal of hES cells under completely chemically defined and xeno-free conditions without ROCK inhibitors. Neither LN-521 nor E-cadherin alone enable clonal survival of hES cells. The LN-521/E-cadherin matrix allows hES cell line derivation from blastocyst inner cell mass and single blastomere cells without a need to destroy the embryo. This method can facilitate the generation of hES cell lines for development of different cell types for regenerative medicine purposes.
|
|
| 10. |
|
|
