| 1. |
- Hallengren, Anders, 1950-
(författare)
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Bulgarisk satir
- 1977
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Ingår i: Litter: tidskrift vid Institutionen för litteraturvetenskap i Stockholm. - 0348-1611. ; :7, s. 2-3
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- Hristo Kolev Pelitev (1927-2012) var en bulgarisk författare och journalist som under åren 1960-1988 var i redaktionen för den humoristiska och satiriska tidningen Stŭrshel (Стършел) som grundats redan 1946 av en grupp vänsterintellektuella. I vådliga skämthistorier och bestickande fabler gycklade "Getingen" med makt och makthavare inom och utom landet i allegorins och seriemagasinets form från folkrepublikens början till dess slut och är nu (2015) landets äldsta tidning.
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| 2. |
- Lidén, Anne, 1947-
(författare)
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Bilder i Pariskommunens tid : Konst, satir och reportage
- 2021
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Ingår i: Förr och nu: tidskrift för en folkets kultur och historia. - 2003-329X. ; :4, s. 1-33
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Denna ikonografiska artikel Bilder i Pariskommunens tid. Konst, satir och reportage i anslutning till 150-årsminnet 2021 bygger på två böcker. John Milners Art, War & Revolution in France 1870-1871 från 2000 utgör en bred översikt av dokument och bildgenrer, såsom historiemåleri, genremåleri, reportagetryck, satiriska tryck och teckningar. Många konstnärers verk och brev redovisas, bl.a. Gustave Courbet. Boken När gatan tog mediemakt. Pariskommunens bilder av Jan Myrdal m.fl. 2016 pesenterar främst de samhällskritiska och satiriska litografiska trycken som tillkom under Pariskommunen och diskuterar dessa bilders roll. Många konstverk och grafiska tryck återges i ikonografiska beskrivningar med illustrationer i färg. Som komplement till dessa två böcker har jag valt att redovisa ny forskning om kvinnornas roll i Pariskommunen samt bilderna i den motpropaganda som riktades mot dem. När det gäller kommunens minne framhävs läraren Louise Michels betydelse i den franska kvinnorörelsen under Pariskommunen.
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| 3. |
- Satir, Tugce Munise, et al.
(författare)
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Accelerated neuronal and synaptic maturation by BrainPhys medium increases Aβ secretion and alters Aβ peptide ratios from iPSC-derived cortical neurons.
- 2020
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- One of the neuropathological hallmarks of Alzheimer's disease (AD) is cerebral deposition of amyloid plaques composed of amyloid β (Aβ) peptides and the cerebrospinal fluid concentrations of those peptides are used as a biomarker for AD. Mature induced pluripotent stem cell (iPSC)-derived cortical neurons secrete Aβ peptides in ratios comparable to those secreted to cerebrospinal fluid in human, however the protocol to achieve mature neurons is time consuming. In this study, we investigated if differentiation of neuroprogenitor cells (NPCs) in BrainPhys medium, previously reported to enhance synaptic function of neurons in culture, would accelerate neuronal maturation and, thus increase Aβ secretion as compared to the conventional neural maintenance medium. We found that NPCs cultured in BrainPhys displayed increased expression of markers for cortical deep-layer neurons, increased synaptic maturation and number of astroglial cells. This accelerated neuronal maturation was accompanied by increased APP processing, resulting in increased secretion of Aβ peptides and an increased Aβ38 to Aβ40 and Aβ42 ratio. However, during long-term culturing in BrainPhys, non-neuronal cells appeared and eventually took over the cultures. Taken together, BrainPhys culturing accelerated neuronal maturation and increased Aβ secretion from iPSC-derived cortical neurons, but changed the cellular composition of the cultures.
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| 4. |
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| 5. |
- Satir, Tugce Munise, et al.
(författare)
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Partial reduction of amyloid β production by β-secretase inhibitors does not decrease synaptic transmission
- 2020
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Ingår i: Alzheimer's Research and Therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Alzheimer's disease (AD) is the most common form of age-related neurodegenerative diseases. Cerebral deposition of Aβ peptides, especially Aβ42, is considered the major neuropathological hallmark of AD and the putative cause of AD-related neurotoxicity. Aβ peptides are produced by sequential proteolytic processing of APP, with β-secretase (BACE) being the initiating enzyme. Therefore, BACE has been considered an attractive therapeutic target in AD research and several BACE inhibitors have been tested in clinical trials, but so far, all have had negative outcomes or even led to worsening of cognitive function. AD can be triggered by Aβ years before the first symptoms appear and one reason for the failures could be that the clinical trials were initiated too late in the disease process. Another possible explanation could be that BACE inhibition alters physiological APP processing in a manner that impairs synaptic function, causing cognitive deterioration. Methods: The aim of this study was to investigate if partial BACE inhibition, mimicking the putative protective effect of the Icelandic mutation in the APP gene, could reduce Aβ generation without affecting synaptic transmission. To investigate this, we used an optical electrophysiology platform, in which effects of compounds on synaptic transmission in cultured neurons can be monitored. We employed this method on primary cortical rat neuronal cultures treated with three different BACE inhibitors (BACE inhibitor IV, LY2886721, and lanabecestat) and monitored Aβ secretion into the cell media. Results: We found that all three BACE inhibitors tested decreased synaptic transmission at concentrations leading to significantly reduced Aβ secretion. However, low-dose BACE inhibition, resulting in less than a 50% decrease in Aβ secretion, did not affect synaptic transmission for any of the inhibitors tested. Conclusion: Our results indicate that Aβ production can be reduced by up to 50%, a level of reduction of relevance to the protective effect of the Icelandic mutation, without causing synaptic dysfunction. We therefore suggest that future clinical trials aimed at prevention of Aβ build-up in the brain should aim for a moderate CNS exposure of BACE inhibitors to avoid side effects on synaptic function. © 2020 The Author(s).
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| 6. |
- Satir, Tugce Munise
(författare)
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The physiological processing of Alzheimer-associated amyloid beta precursor protein in human and animal-derived neuronal models
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Alzheimer’s disease (AD) is characterized by cognitive impairment due to the loss of structure and/or function of neurons, and amyloid plaques composed of aggregated-amyloid beta (Aβ) peptides, primarily species ending at the amino acid 42 (Aβ42), are one of the major neuropathological hallmarks of AD. Aβ peptides of different lengths are produced by sequential cleavage of amyloid beta precursor protein (APP) by α-, β- and γ- secretases. Aβ peptides are often considered “toxic”, but they are also involved in many biological processes such as neuronal differentiation and synaptic activity. Therefore, this thesis aims to increase the understanding of APP and Aβ regulations by investigating when, where and how APP is processed in cortical neurons and how this is linked to neuronal maturation and synaptic activity. In Project I, we measured secreted Aβ peptides during cortical differentiation of human induced pluripotent stem cells (iPSCs) and showed that APP processing changes during differentiation. In neuroprogenitor cells (NPCs), APP is predominantly processed via the non-amyloidogenic pathway (α-/β-secretase) producing short Aβ peptides, whereas with the formation of a neuronal phenotype and increased synaptic function, the processing of APP shifts towards the amyloidogenic pathway (β-/γ-secretase) producing longer Aβ peptides. Next, we hypothesized that secretion of the longer, potentially amyloidogenic Aβ peptides requires a neuronal phenotype-dependent co-localization of APP and APP-cleaving enzymes. Project II thus aimed at investigating if co-localization of APP with APP-cleaving enzymes could explain the changes in Aβ secretion. We showed that APP co-localization with PSEN1 (γ-secretase) correlated with secretion of the longer Aβ peptides, supporting our initial hypothesis. In Project III, we differentiated the NPCs in a culture medium designed to increase synaptic activity, to investigate the effects of accelerated neuronal and synaptic maturity on APP processing, and showed that increased neuronal maturity and activity increased the secretion of Aβ peptides along with sAPPα/β. We also showed that the secretion of Aβ peptides in our model was regulated in part, but not entirely, by synaptic activity. In Project IV, we investigated if reducing Aβ secretion by inhibiting APP-cleaving enzymes would affect synaptic transmission and showed that reduction in Aβ42 exceeding 50% decreased synaptic transmission, suggesting that Aβ42 (or altered APP processing) may have a regulatory effect on the synaptic activity in a concentration-dependent manner. In conclusion, we found that APP is differentially processed depending on neuronal and synaptic maturation and presented a platform for future studies targeting APP/Aβ function and dysfunction.
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| 9. |
- Banote, Rakesh Kumar, et al.
(författare)
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Amyloid precursor protein-b facilitates cell adhesion during early development in zebrafish
- 2020
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Understanding the biological function of amyloid beta (A beta) precursor protein (APP) beyond its role in Alzheimer's disease is emerging. Yet, its function during embryonic development is poorly understood. The zebrafish APP orthologue, Appb, is strongly expressed during early development but thus far has only been studied via morpholino-mediated knockdown. Zebrafish enables analysis of cellular processes in an ontogenic context, which is limited in many other vertebrates. We characterized zebrafish carrying a homozygous mutation that introduces a premature stop in exon 2 of the appb gene. We report that appb mutants are significantly smaller until 2 dpf and display perturbed enveloping layer (EVL) integrity and cell protrusions at the blastula stage. Moreover, appb mutants surviving beyond 48 hpf exhibited no behavioral defects at 6 dpf and developed into healthy and fertile adults. The expression of the app family member, appa, was also found to be altered in appb mutants. Taken together, we show that appb is involved in the initial development of zebrafish by supporting the integrity of the EVL, likely by mediating cell adhesion properties. The loss of Appb might then be compensated for by other app family members to maintain normal development.
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| 10. |
- Bergström, Petra, et al.
(författare)
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Amyloid precursor protein expression and processing are differentially regulated during cortical neuron differentiation
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Amyloid precursor protein (APP) and its cleavage product amyloid beta (A beta) have been thoroughly studied in Alzheimer's disease. However, APP also appears to be important for neuronal development. Differentiation of induced pluripotent stem cells (iPSCs) towards cortical neurons enables in vitro mechanistic studies on human neuronal development. Here, we investigated expression and proteolytic processing of APP during differentiation of human iPSCs towards cortical neurons over a 100-day period. APP expression remained stable during neuronal differentiation, whereas APP processing changed. alpha-Cleaved soluble APP (sAPP alpha) was secreted early during differentiation, from neuronal progenitors, while beta-cleaved soluble APP (sAPP beta) was first secreted after deep-layer neurons had formed. Short A beta peptides, including A beta 1-15/16, peaked during the progenitor stage, while processing shifted towards longer peptides, such as A beta 1-40/42, when post-mitotic neurons appeared. This indicates that APP processing is regulated throughout differentiation of cortical neurons and that amyloidogenic APP processing, as reflected by A beta 1-40/42, is associated with mature neuronal phenotypes.
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