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| 2. |
- Beretta, Chiara, et al.
(författare)
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Astrocytes with Alzheimer’s disease pathology provoke lipid droplet mediated cell-to-cell propagation of MHC II complexes
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background. Astrocytes are critical for maintaining brain homeostasis, but are also highly involved in neuroinflammation. In the Alzheimer disease (AD) brain, reactive, inflammatory astrocytes are situated closely around amyloid β (Aβ) plaques. We have previously shown that reactive astrocytes ingest large quantities of soluble Aβ aggregates, but are unable to degrade the material, which leads to intracellular Aβ accumulation and severe cellular stress. A common response to cellular stress is the formation of lipid droplets (LDs). Novel data indicate that LDs play an important role in inflammatory processes. However, the involvement of LDs in AD inflammation and progression remains unclear.Methods. The aim of this study was to investigate how astrocytic Aβ pathology affects lipid metabolism and antigen presentation. For this purpose, human induced pluripotent stem cell (iPSC) derived astrocytes were exposed to soluble Aβ42 aggregates and analyzed over time, using a battery of experimental approaches.Results. Our results show that Aβ exposure induces LD accumulation in astrocytes, although the overall lipid composition remains unchanged. Moreover, astrocytes transfer LDs to neighboring cells via tunneling nanotubes (TNTs) and extracellular vesicle (EVs). Interestingly, we found that the antigen presenting protein major histocompatibility complex II (MHCII) is present inside LDs, suggesting an active role of LDs in astrocytic antigen presentation. Immunohistochemical analysis of human brain tissue verified the presence of LD-loaded MHCII+ astrocytes in AD individuals. Moreover, we found infiltrated CD4+ T cells to be in close contact with astrocytes, confirming an astrocyte T cell cross-talk in the AD brainConclusions. Taken together, our data show that Aβ pathology drastically affects lipid storage in astrocytes, which in turn modulates the astrocytic antigen presentation, indicating a role for astrocytic LDs in T cell responses in the AD brain.
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| 3. |
- Bhalerao, Rupali, et al.
(författare)
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Gene expression in autumn leaves
- 2003
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Ingår i: Plant Physiology. - : Oxford University Press (OUP). - 0032-0889 .- 1532-2548. ; 131:2, s. 430-442
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Tidskriftsartikel (refereegranskat)abstract
- Two cDNA libraries were prepared, one from leaves of a field-grown aspen (Populus tremula) tree, harvested just before any visible sign of leaf senescence in the autumn, and one from young but fully expanded leaves of greenhouse-grown aspen (Populus tremula X tremuloides). Expressed sequence tags (ESTs; 5,128 and 4,841, respectively) were obtained from the two libraries. A semiautomatic method of annotation and functional classification of the ESTs, according to a modified Munich Institute of Protein Sequences classification scheme, was developed, utilizing information from three different databases. The patterns of gene expression in the two libraries were strikingly different. In the autumn leaf library, ESTs encoding metallothionein, early light-inducible proteins, and cysteine proteases were most abundant. Clones encoding other proteases and proteins involved in respiration and breakdown of lipids and pigments, as well as stress-related genes, were also well represented. We identified homologs to many known senescence-associated genes, as well as seven different genes encoding cysteine proteases, two encoding aspartic proteases, five encoding metallothioneins, and 35 additional genes that were up-regulated in autumn leaves. We also indirectly estimated the rate of plastid protein synthesis in the autumn leaves to be less that 10% of that in young leaves.
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| 4. |
- Bratteby, Klas, et al.
(författare)
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In Vivo Veritas : 18F-Radiolabeled Glycomimetics Allow Insights into the Pharmacological Fate of Galectin-3 Inhibitors
- 2020
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Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 63:2, s. 747-755
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Tidskriftsartikel (refereegranskat)abstract
- Glycomimetic drugs have attracted increasing interest as unique targeting vectors or surrogates for endogenous biomolecules. However, it is generally difficult to determine the in vivo pharmacokinetic profile of these compounds. In this work, two galectin-3 inhibitors were radiolabeled with fluorine-18 and used as surrogate PET tracers of TD139 and GB1107. Both compounds are promising drugs for clinical applications. In vivo evaluation revealed that both surrogates strongly differed with respect to their biodistribution profile. The disaccharide (TD139 surrogate) was rapidly eliminated from blood while the monosaccharide (GB1107 surrogate) showed no sign of excretion. The data obtained allowed us to infer the different in vivo fate of TD139 and GB1107 and rationalize how different administration routes could boost efficacy. Whereas the fast excretion profile of the TD139 surrogate indicated that systemic application of disaccharides is unfavorable, the extended biological half-life of the GB1107 surrogate indicated that systemic administration is possible for monosaccharides.
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| 6. |
- Clausen, Fredrik, et al.
(författare)
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Combination of growth factor treatment and scaffold deposition following traumatic brain injury has only a temporary effect on regeneration
- 2014
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Ingår i: Brain Research. - : Elsevier BV. - 0006-8993 .- 1872-6240. ; 1588, s. 37-48
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Tidskriftsartikel (refereegranskat)abstract
- The recovery after traumatic brain injury (TBI) is hampered by the poor regenerative capacity of the brain. Today there is no treatment available that effectively restores lost brain tissue, but much research is focused on the stimulation of endogenous neural stem cells to viably and functionally repopulate the injured parenchyma. It is crucial that the therapies have a proven long-term effect on both regeneration and functional recovery to be clinically interesting. Here we have studied the induction of stem cell activation in rats at three weeks and six weeks after inducing TBI using controlled cortical impact model at a severe setting. We combined intracerebroventricular growth factor and scaffold treatment in order to accomplish an optimal effect on the stem cell regeneration. Immediately after TBI epidermal growth factor infusion with osmotic minipumps was started and continued for seven days. The pumps were removed and an extracellular matrix scaffold containing vascular endothelial growth factor was deposited into the cortical cavity. Three weeks after injury there was a positive effect of the treatment with a significant increase in neuronal and astrocytic regeneration. However, after six weeks there was no difference in the number of newly generated neurons and astrocytes in treated or untreated rats. Evaluation of tissue loss and spatial learning in the Morris water maze corroborated that the treatment had no effect at the later time point. Our results highlight the importance of long-term studies to ensure that a promising effect on tissue regeneration and functional outcome is not only temporary.
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| 7. |
- Dahlgren, Liselotte, et al.
(författare)
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Differences in human papillomavirus type may influence clinical outcome in early stage cervical cancer.
- 2006
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Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 26:2A, s. 829-32
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The presence of human papillomavirus (HPV), the HPV type and viral load in early stage cervical carcinoma were investigated in order to elucidate whether any of these factors were important for clinical outcome. PATIENTS AND METHODS: Twelve patients who were disease-free 5 years after diagnosis were matched and compared with 12 patients who died within 2 years. The presence of HPV, HPV type and viral load in their tumours was examined by PCR. RESULTS: The distribution and load of HPV was similar in the 2 patient groups. HPV-16 was, however, significantly more common in tumours of the surviving patients than in those of patients who died (88.9% and 18.2%, respectively, p = 0.0152). CONCLUSION: HPV-16 was significantly more common in early stage carcinomas of patients surviving more than 5 years in comparison to early stage carcinomas of patients with a poor prognosis.
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| 8. |
- ERLANDSSON, ARVID, et al.
(författare)
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Choice-justifications after allocating resources in helping dilemmas
- 2017
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Ingår i: Judgment and Decision Making. - : SOC JUDGMENT & DECISION MAKING. - 1930-2975. ; 12:1, s. 60-80
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Tidskriftsartikel (refereegranskat)abstract
- How do donors reason and justify their choices when faced with dilemmas in a charitable context? In two studies, Swedish students were confronted with helping dilemmas based on the identifiable victim effect, the proportion dominance effect and the ingroup effect. Each dilemma consisted of two comparable charity projects and participants were asked to choose one project over the other. They were then asked to provide justifications of their choice by stating the relative importance of different types of reasons. When faced with an identified victim dilemma, participants did not choose the project including an identified victim more often than the project framed statistically, but those who did emphasized emotional reasons (e.g., “Because I had more empathic feelings”), but not any other reasons, more than those choosing the statistical project. When faced with a Proportion dominance dilemma, participants more often chose the project with a high rescue proportion (e.g., you can save 100% out of 30) than the project with a low rescue proportion (e.g., you can save 4% out of 800), and those who did emphasized efficacy reasons (e.g., “Because my money can make a greater difference there”), but no other reasons, more than those favoring the low recue proportion project. Finally, when faced with an Ingroup dilemma, participants more often chose the project that could help ingroup-victims over the project that could help outgroup victims, and those who did emphasized responsibility reasons (e.g., “Because I have a greater obligation”), but no other reasons, more than those favoring outgroup projects. These results are consistent with and extend previous findings about how different helping effects are related to different psychological processes.
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| 9. |
- Erlandsson, Arvid, et al.
(författare)
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Emotional reactions, perceived impact and perceived responsibility mediate the identifiable victim effect, proportion dominance effect and in-group effect respectively
- 2015
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Ingår i: Organizational Behavior and Human Decision Processes. - : Elsevier BV. - 0749-5978 .- 1095-9920. ; 127:March, s. 1-14
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Tidskriftsartikel (refereegranskat)abstract
- This study investigated possible mediators of the identifiable victim effect (IVE), the proportion dominance effect (PDE), and the in-group effect (IGE) in helping situations. In Studies 1-3, participants rated their emotional reactions (distress and sympathy toward the victims), perceived impact of helping, perceived responsibility to help, and helping motivation toward four versions of a helping situation. Gradually increasing victim identifiability in the helping situations primarily affected emotional reactions and sympathy completely mediated the IVE. Gradually making the reference-group smaller primarily affected perceived impact, and impact completely mediated the PDE. Gradually increasing in-groupness primarily affected perceived responsibility, and responsibility completely mediated the IGE. Study 4 included real monetary allocations and largely replicated the results using a between-subject design. Together, the results shed light on how contextual factors trigger help motivation, and indicate that different helping effects are primarily mediated by different mechanisms.
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