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A guide to Strategic Partnerships : Structure collaboration between academia and wider society
- 2020
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Editorial collection (pop. science, debate, etc.)abstract
- To facilitate work on strategic partnerships, 16 higher education institutions in Sweden have produced a guide, within a partnership with funding from Vinnova. The “Strategic Partnership Guide” is a description of and a guide to strategic partnerships. It is formulated from the perspective of a higher education institution. The target group is staff working with collaboration in the area of operational support at Swedish universities and colleges, to provide support in their professional role. The guide may also be useful for vice-chancellors, management teams at higher education institutions, executive boards or academic leaders, to help familiarise themselves with this kind of collaboration. The guide provides an introduction to strategic partnerships and compiles experiences and lessons learned that can facilitate work when getting started with or further developing partnerships.
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| 2. |
- Adlerz, Linda, 1974-
(author)
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Processing of the amyloid precursor protein and its paralogues amyloid precursor-like proteins 1 and 2
- 2007
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Doctoral thesis (other academic/artistic)abstract
- Alzheimer’s disease (AD) is a neurodegenerative disorder which is histopathologically characterised by amyloid plaques and neurofibrillary tangles. Amyloid plaques consist of the amyloid β-peptide (Aβ) that can form aggregates in the brain. Aβ is generated from the amyloid precursor protein (APP) through proteolytic cleavage. APP belongs to a conserved protein family that also includes the two paralogues, APP-like proteins 1 and 2 (APLP1 and APLP2). Despite the immense amount of research on APP, motivated by its implication in AD, the function of this protein family has not yet been determined. In this thesis, we have studied the expression and proteolytic processing of the APP protein family. Our results are consistent with previous findings that suggest a role for APP during neuronal development. Treatment of cells with retinoic acid (RA) resulted in increased synthesis. In addition, we observed that RA treatment shifted the processing of APP from the amyloidogenic to the non-amyloidogenic pathway. The proteins in the APP family have been hard to distinguish both with respect to function and proteolytic processing. However, for development of new drugs with APP processing enzymes as targets this is of great importance. Our studies suggest similarities, but also differences in the mechanism regulating the processing of the different paralogues. We found that brain-derived neurotrophic factor (BDNF) had different impact on the members of the APP family. Most interestingly, we also found that the mechanism behind the increased processing in response to IGF-1 was not identical between the homologous proteins. In summary, our results indicate that in terms of regulation APLP1 and APLP2 differ more from each other than from APP. Our studies open up the possibility of finding means to selectively block Aβ production without interfering with the processing and function of the paralogous proteins.
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| 3. |
- Gumucio, Astrid, 1983-
(author)
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Therapeutic and functional studies in animal models of Alzheimer's disease
- 2014
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Doctoral thesis (other academic/artistic)abstract
- Senile plaques (Aβ) and neurofibrillary tangles (tau) are pathological hallmarks of Alzheimer’s disease (AD). If and how the formation of these deposits are mechanistically linked remains mainly unknown. In recent years, the focus has shifted from insoluble protein deposits to soluble aggregates of Aβ and tau. Protofibrils are large soluble Aβ oligomers which were linked to AD by the discovery of the Arctic AβPP mutation.Treatment of young tg-ArcSwe mice with an Aβ protofibril-selective antibody, mAb158, cleared protofibrils, prevented amyloid plaque deposition and protected cultured cells from protofibril-mediated toxicity. This suggests that Aβ protofibrils are necessary for the formation of Aβ deposits. Functional assessment of tg-ArcSwe mice in IntelliCage demonstrated hippocampal-dependent behavioral deficits such as memory/learning impairments, hyperactivity and perseverance behavior. Learning impairments did not correlate to Aβ-measures but to calbindin, which might be a good marker for Aβ-mediated neuronal dysfunction.Splicing of exon 10 in the tau gene differs between human and mouse brain. Exon 10 is part of the microtubule-binding domains which helps to maintain microtubule stability and axonal transport, functions vital to neuronal viability. Axonal transport dysfunction has been proposed as a common pathway of Aβ and tau pathogenesis in AD. Generation of a novel tau mouse model with absence of exon 10 led to age-dependent sensorimotor impairments which may relate to dysfunctions in cerebellum. No tau pathology was evident suggesting that a trigger of tau fibrillization e.g. a human Aβ or tau aggregate is needed. Generation of AβPPxE10 bitransgenic mice with no exon 10 showed lower Aβ plaque burden. Possibly changes in microtubule function lead to altered intracellular AβPP transport and Aβ production. Initiation of tau pathology in AβPPxE10 mice might require a certain type of Aβ-aggregates which is not produced or exist at too low concentration in transgenic mouse brain.In summary, the Aβ protofibril-selective antibody was found to be a promising treatment for AD. The IntelliCage system was proven to be useful for functional evaluation of AβPP mice. Exon 10 in tau was shown to affect sensorimotor functions and Aβ pathology in bitransgenic mice by mechanisms that deserve further investigation.
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| 4. |
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Handledning för strategiska partnerskap : Strukturerad samverkan mellan akademin och det omgivande samhället
- 2020
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Editorial collection (pop. science, debate, etc.)abstract
- För att underlätta arbetet med strategiska partnerskap har 16 lärosäten i Sverige tagit fram en handledning, inom ett samarbete med finansiering från Vinnova. “Handledning för strategiska partnerskap” är en beskrivning av och vägledning till strategiska partnerskap. Den är formulerad ur ett lärosätes perspektiv. Målgruppen är personal som arbetar med samverkan inom verksamhetsstöd vid svenska universitet och högskolor, som ett stöd i deras yrkesutövning. Men även rektorer, lärosätesledningar, styrelser och akademiska ledare kan ha användning av handledningen, för att sätta sig in i villkoren för denna typ av samverkan. Handledningen ger en introduktion till strategiska partnerskap och samlar erfarenheter och lärdomar som kan underlätta arbetet att komma igång med eller vidareutveckla partnerskap.
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| 5. |
- Zheng, Lin, et al.
(author)
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Macroautophagy-generated increase of lysosomal amyloid beta-protein mediates oxidant-induced apoptosis of cultured neuroblastoma cells
- 2011
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In: Autophagy. - : Informa UK Limited. - 1554-8627 .- 1554-8635. ; 7:12, s. 1528-1545
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Journal article (peer-reviewed)abstract
- Increasing evidence suggests the toxicity of intracellular amyloid beta-protein (A beta) to neurons, as well as the involvement of oxidative stress in Alzheimer disease (AD). Here we show that normobaric hyperoxia (exposure of cells to 400/c oxygen for five days, and consequent activation of macroautophagy and accumulation of A beta within lysosomes, induced apoptosis in differentiated SH-SY5Y neuroblastoma cells. Cells under hyperoxia showed: (1) increased numbers of autophagic vacuoles that contained amyloid precursor protein (APP) as well as A beta monomers and oligomers, (2) increased reactive oxygen species production, and (3) enhanced apoptosis. Oxidant-induced apoptosis positively correlated with cellular A beta production, being the highest in cells that were stably transfected with APP Swedish KM670/671NL double mutation. Inhibition of v-secretase, prior and/or in parallel to hyperoxia, suggested that the increase of lysosomal A beta resulted mainly from its autophagic uptake, but also from APP processing within autophagic vacuoles. The oxidative stress-mediated effects were prevented by macroautophagy inhibition using 3-methyladenine or ATG5 downregulation. Our results suggest that upregulation of macroautophagy and resulting lysosomal A beta accumulation are essential for oxidant-induced apoptosis in cultured neuroblastoma cells and provide additional support for the interactive role of oxidative stress and the lysosomal system in AD-related neurodegeneration.
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| 6. |
- Zheng, Lin, et al.
(author)
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Macroautophagy-generated increase of lysosomal amyloid β-protein mediates oxidant-induced apoptosis of cultured neuroblastoma cells
- 2011
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In: Autophagy. - : Landes Bioscience. - 1554-8627 .- 1554-8635. ; 7:12, s. 1528-1545
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Journal article (peer-reviewed)abstract
- Increasing evidence suggests the toxicity of intracellular amyloid β-protein (Aβ) to neurons, as well as the involvement of oxidative stress in Alzheimer disease (AD). Here we show that normobaric hyperoxia (exposure of cells to 40% oxygen for five days, and consequent activation of macroautophagy and accumulation of Aβ within lysosomes, induced apoptosis in differentiated SH-SY5Y neuroblastoma cells. Cells under hyperoxia showed: (1) increased numbers of autophagic vacuoles that contained amyloid precursor protein (APP) as well as Aβ monomers and oligomers, (2) increased reactive oxygen species production, and (3) enhanced apoptosis. Oxidant-induced apoptosis positively correlated with cellular Aβ production, being the highest in cells that were stably transfected with APP Swedish KM670/671NL double mutation. Inhibition of γ-secretase, prior and/or in parallel to hyperoxia, suggested that the increase of lysosomal Aβ resulted mainly from its autophagic uptake, but also from APP processing within autophagic vacuoles. The oxidative stress-mediated effects were prevented by macroautophagy inhibition using 3-methyladenine or ATG5 downregulation. Our results suggest that upregulation of macroautophagy and resulting lysosomal Aβ accumulation are essential for oxidant-induced apoptosis in cultured neuroblastoma cells and provide aditional support for the interactive role of oxidative stress and the lysosomal system in AD-related neurodegeneration.
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| 7. |
- Zheng, Lin, et al.
(author)
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Oxidative stress induces macroautophagy of amyloid beta-protein and ensuing apoptosis
- 2009
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In: Free Radical Biology & Medicine. - : Elsevier BV. - 0891-5849 .- 1873-4596. ; 46:3, s. 422-429
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Journal article (peer-reviewed)abstract
- There is increasing evidence for the toxicity of intracellular amyloid beta-protein (A beta) to neurons and the involvement of lysosomes in this process in Alzheimer disease (AD). We have recently shown that oxidative stress, a recognized determinant of AD. enhances macroautophagy and leads to intralysosomal accumulation of A beta in Cultured neuroblastoma cells. We hypothesized that oxidative stress promotes AD by stimulating macroautophagy of A that further may induce cell death by destabilizing lysosomal membranes. To investigate such possibility, we compared the effects of hyperoxia (40% ambient oxygen) in cultured HEK293 cells that were transfected with an empty vector (Vector), wild-type APP (APPwt), or Swedish mutant APP (APPswe). Exposure to hyperoxia for 5 days increased the number of cells with A beta-containing lysosomes, as well as the number of apoptotic cells, compared to normoxic conditions. The rate of apoptosis in all three cell lines demonstrated dependence on intralysosomal A beta content (Vector
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