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| 2. |
- Hofvander Trulsson, Ylva, et al.
(författare)
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Inkluderande pedagogik.
- 2018
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Ingår i: Skapande och integration. - 9789144120706 ; , s. 15-35
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Bokkapitel (refereegranskat)
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| 3. |
- Hofvander Trulsson, Ylva, et al.
(författare)
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”Romer är de enda sanna européerna”
- 2018
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Ingår i: Skapande och Integration. - 9789144120706 ; , s. 137-148
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 4. |
- Aits, Sonja, et al.
(författare)
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HAMLET (human alpha-lactalbumin made lethal to tumor cells) triggers autophagic tumor cell death.
- 2009
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 124:5, s. 1008-1019
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Tidskriftsartikel (refereegranskat)abstract
- HAMLET, a complex of partially unfolded alpha-lactalbumin and oleic acid, kills a wide range of tumor cells. Here we propose that HAMLET causes macroautophagy in tumor cells and that this contributes to their death. Cell death was accompanied by mitochondrial damage and a reduction in the level of active mTOR and HAMLET triggered extensive cytoplasmic vacuolization and the formation of double-membrane-enclosed vesicles typical of macroautophagy. In addition, HAMLET caused a change from uniform (LC3-I) to granular (LC3-II) staining in LC3-GFP-transfected cells reflecting LC3 translocation during macroautophagy, and this was blocked by the macroautophagy inhibitor 3-methyladenine. HAMLET also caused accumulation of LC3-II detected by Western blot when lysosomal degradation was inhibited suggesting that HAMLET caused an increase in autophagic flux. To determine if macroautophagy contributed to cell death, we used RNA interference against Beclin-1 and Atg5. Suppression of Beclin-1 and Atg5 improved the survival of HAMLET-treated tumor cells and inhibited the increase in granular LC3-GFP staining. The results show that HAMLET triggers macroautophagy in tumor cells and suggest that macroautophagy contributes to HAMLET-induced tumor cell death.
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| 5. |
- Aldrin, Emilia, 1982-, et al.
(författare)
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Socioonomastiska perspektiv på personnamn, djurnamn och företagsnamn : fem smärre studier
- 2017
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Ingår i: Ortnamnssällskapet i Uppsala årsskrift. - Uppsala : Ortnamnssällskapet i Uppsala. - 0473-4351. ; , s. 5-13
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- This article presents five undergraduate dissertations in socio-onomastics written by students from Halmstad University in 2016 and presented during a visit to the Department of Scandinavian Languages, Scandinavian Onomastics, at Uppsala University in 2017. Two of the dissertations deal with personal names (a social constructionist approach to personal names in children’s literature, and perceptions of name and identity among senior citizens). Two others focus on animal names in contemporary times (a gender analysis of names of horses, and a comparative analysis of names within different dog breeds). The last undergraduate dissertation concerns the process of naming companies.
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| 6. |
- Andersson, Gunvor, et al.
(författare)
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Missbrukande föräldrar, utsatta barn och socialt arbete
- 2006
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Ingår i: Nordic Studies on Alcohol and Drugs. - 1458-6126. ; 23:1, s. 45-56
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The aim of the article is to put together four different studies and research perspectives. The four authors present their own studies about drug addicted mothers; fathers called into question by child welfare authorities; children in foster care; child welfare services. The four studies have a qualitative approach, interviewing parents and children in vulnerable positions and in contact with child welfare authorities. The combined results show the need of coooperation between child welfare and rehabilitation of adults addicted to alcohol and drugs, and the need to have a comprehensive approach to vulnerable families, also during separation. The right of vulnerable children to be heard in research as well as in practice is exemplified and emphasized.
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| 7. |
- Gustafsson, Lotta, et al.
(författare)
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Changes in proteasome structure and function caused by HAMLET in tumor cells.
- 2009
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 4:4
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Proteasomes control the level of endogenous unfolded proteins by degrading them in the proteolytic core. Insufficient degradation due to altered protein structure or proteasome inhibition may trigger cell death. This study examined the proteasome response to HAMLET, a partially unfolded protein-lipid complex, which is internalized by tumor cells and triggers cell death. METHODOLOGY/PRINCIPAL FINDINGS: HAMLET bound directly to isolated 20S proteasomes in vitro and in tumor cells significant co-localization of HAMLET and 20S proteasomes was detected by confocal microscopy. This interaction was confirmed by co-immunoprecipitation from extracts of HAMLET-treated tumor cells. HAMLET resisted in vitro degradation by proteasomal enzymes and degradation by intact 20S proteasomes was slow compared to fatty acid-free, partially unfolded alpha-lactalbumin. After a brief activation, HAMLET inhibited proteasome activity in vitro and in parallel a change in proteasome structure occurred, with modifications of catalytic (beta1 and beta5) and structural subunits (alpha2, alpha3, alpha6 and beta3). Proteasome inhibition was confirmed in extracts from HAMLET-treated cells and there were indications of proteasome fragmentation in HAMLET-treated cells. CONCLUSIONS/SIGNIFICANCE: The results suggest that internalized HAMLET is targeted to 20S proteasomes, that the complex resists degradation, inhibits proteasome activity and perturbs proteasome structure. We speculate that perturbations of proteasome structure might contribute to the cytotoxic effects of unfolded protein complexes that invade host cells.
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| 8. |
- Ho Cs, James, et al.
(författare)
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HAMLET: functional properties and therapeutic potential.
- 2012
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Ingår i: Future Oncology. - : Future Medicine Ltd. - 1479-6694 .- 1744-8301. ; 8:10, s. 1301-1313
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Tidskriftsartikel (refereegranskat)abstract
- Human α-lactalbumin made lethal to tumor cells (HAMLET) is the first member in a new family of protein-lipid complexes that kills tumor cells with high selectivity. The protein component of HAMLET is α-lactalbumin, which in its native state acts as a substrate specifier in the lactose synthase complex, thereby defining a function essential for the survival of lactating mammals. In addition, α-lactalbumin acquires tumoricidal activity after partial unfolding and binding to oleic acid. The lipid cofactor serves the dual role as a stabilizer of the altered fold of the protein and a coactivator of specific steps in tumor cell death. HAMLET is broadly tumoricidal, suggesting that the complex identifies conserved death pathways suitable for targeting by novel therapies. Sensitivity to HAMLET is defined by oncogene expression including Ras and c-Myc and by glycolytic enzymes. Cellular targets are located in the cytoplasmic membrane, cytoskeleton, mitochondria, proteasomes, lysosomes and nuclei, and specific signaling pathways are rapidly activated, first by interactions of HAMLET with the cell membrane and subsequently after HAMLET internalization. Therapeutic effects of HAMLET have been demonstrated in human skin papillomas and bladder cancers, and HAMLET limits the progression of human glioblastomas, with no evidence of toxicity for normal brain or bladder tissue. These findings open up new avenues for cancer therapy and the understanding of conserved death responses in tumor cells.
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| 9. |
- Pettersson, Jenny, et al.
(författare)
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alpha-Lactalbumin, Engineered to be Non-native and Inactive, Kills Tumor Cells when in Complex with Oleic Acid: A new biological function resulting from partial unfolding.
- 2009
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Ingår i: Journal of Molecular Biology. - : Elsevier BV. - 1089-8638 .- 0022-2836. ; 394:5, s. 994-1010
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Tidskriftsartikel (refereegranskat)abstract
- HAMLET (human alpha-lactalbumin made lethal to tumor cells) is a tumoricidal complex consisting of partially unfolded protein and fatty acid, and was first identified in casein fractions of human breast milk. The complex can be produced from its pure components through a modified chromatographic procedure where pre-applied oleic acid binds with partially-unfolded alpha-lactalbumin on the stationary phase in situ. Because native alpha-lactalbumin itself cannot trigger cell death, HAMLET's remarkable tumor-selective cytotoxicity has been strongly correlated with the conformational change of the protein upon forming the complex, but whether a recovery to the native state subsequently occurs upon entering the tumor cell is yet unclear. To this end, we utilize a recombinant variant of human alpha-lactalbumin in which all eight cysteine residues are substituted for alanines (rHLA(all-Ala)), rendering the protein non-native and biologically inactive under all conditions. The HAMLET analogue formed from the complex of rHLA(all-Ala) and oleic acid (rHLA(all-Ala)-OA) exhibited equivalent strong tumoricidal activity against lymphoma and carcinoma cell lines, and was shown to accumulate within the nuclei of tumor cells, thus reproducing the cellular trafficking pattern of HAMLET. In contrast, the fatty acid-free rHLA(all-Ala) protein associated with the tumor cell surface but was not internalized and lacked any cytotoxic activity. Structurally, whereas HAMLET exhibited some residual native character in terms of NMR chemical shift dispersion, rHLA(all-Ala)-OA showed significant differences to HAMLET, and in fact was found to be devoid of any tertiary packing. The results identify alpha-lactalbumin as a protein with strikingly different functions in the native and partially unfolded states. We posit that partial unfolding offers another significant route of functional diversification for proteins within the cell.
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| 10. |
- Pettersson, Jenny, et al.
(författare)
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Can misfolded proteins be beneficial? The HAMLET case.
- 2009
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Ingår i: Annals of Medicine. - : Informa UK Limited. - 1365-2060 .- 0785-3890. ; 41, s. 162-176
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Forskningsöversikt (refereegranskat)abstract
- By changing the three-dimensional structure, a protein can attain new functions, distinct from those of the native protein. Amyloid-forming proteins are one example, in which conformational change may lead to fibril formation and, in many cases, neurodegenerative disease. We have proposed that partial unfolding provides a mechanism to generate new and useful functional variants from a given polypeptide chain. Here we present HAMLET (Human Alpha-lactalbumin Made LEthal to Tumor cells) as an example where partial unfolding and the incorporation of cofactor create a complex with new, beneficial properties. Native alpha-lactalbumin functions as a substrate specifier in lactose synthesis, but when partially unfolded the protein binds oleic acid and forms the tumoricidal HAMLET complex. When the properties of HAMLET were first described they were surprising, as protein folding intermediates and especially amyloid-forming protein intermediates had been regarded as toxic conformations, but since then structural studies have supported functional diversity arising from a change in fold. The properties of HAMLET suggest a mechanism of structure-function variation, which might help the limited number of human protein genes to generate sufficient structural diversity to meet the diverse functional demands of complex organisms.
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