| 1. |
- Gustafsson, Erika, et al.
(författare)
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Directed evolution of chemotaxis inhibitory protein of Staphylococcus aureus generates biologically functional variants with reduced interaction with human antibodies
- 2010
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Ingår i: Protein Engineering Design & Selection. - : Oxford University Press (OUP). - 1741-0126 .- 1741-0134. ; 23:2, s. 91-101
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Tidskriftsartikel (refereegranskat)abstract
- Chemotaxis inhibitory protein of Staphylococcus aureus (CHIPS) is a protein that binds and blocks the C5a receptor (C5aR) and formylated peptide receptor, thereby inhibiting the immune cell recruitment associated with inflammation. If CHIPS was less reactive with existing human antibodies, it would be a promising anti-inflammatory drug candidate. Therefore, we applied directed evolution and computational/rational design to the CHIPS gene in order to generate new CHIPS variants displaying lower interaction with human IgG, yet retaining biological function. The optimization was performed in four rounds: one round of random mutagenesis to add diversity into the CHIPS gene and three rounds of DNA recombination by Fragment INduced Diversity (FIND((R))). Every round was screened by phage selection and/or ELISA for decreased interaction with human IgG and retained C5aR binding. The mean binding of human anti-CHIPS IgG decreased with every round of evolution. For further optimization, new amino acid substitutions were introduced by rational design, based on the mutations identified during directed evolution. Finally, seven CHIPS variants with low interaction with human IgG and retained C5aR blocking capacity could be identified.
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| 2. |
- Larsson, Jimmy, et al.
(författare)
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Nuclear receptor binding protein 2 is induced during neural progenitor differentiation and affects cell survival
- 2008
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Ingår i: Molecular and Cellular Neuroscience. - : Elsevier BV. - 1044-7431 .- 1095-9327. ; 39:1, s. 32-9
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Tidskriftsartikel (refereegranskat)abstract
- We previously identified nuclear receptor binding protein 2 (NRBP2) in a screen for genes induced by differentiation of neural stem/progenitor cells. Here we show that during embryonic mouse brain development NRBP2 was expressed in the walls of the third and fourth ventricles, and in the hippocampus. In the adult brain, Purkinje cells of the cerebellum and neurons in the CA3 region of the hippocampus were main sites of NRBP2 expression. Analysis of a pediatric medulloblastoma showed that clusters of NRBP2 positive tumor cells co-expressed neurofilament, but not GFAP. Thus, NRBP2 was associated with neuronal differentiation both in normal and malignant brain tissue. We report that NRBP2 is a 55-60 kDa protein with mainly cytoplasmic location. In vitro, NRBP2 protein levels increased as neural stem/progenitor cells differentiated, and its down regulation by siRNA rendered neural progenitor cells more vulnerable to apoptosis. NRBP2 has no previously assigned function and our studies suggest a role for NRBP2 in neural progenitor cell survival.
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| 3. |
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| 4. |
- Bergemalm, Daniel, 1977-, et al.
(författare)
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Changes in the spinal cord proteome of an amyotrophic lateral sclerosis murine model determined by differential in-gel electrophoresis
- 2009
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Ingår i: Molecular and cellular proteomics. - : The American Society for Biochemistry and Molecular Biology,Inc. - 1535-9484. ; 8:6, s. 1306-1317
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Tidskriftsartikel (refereegranskat)abstract
- Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by loss of motor neurons resulting in progressive paralysis. To date, more than 140 different mutations in the gene encoding CuZn-superoxide dismutase (SOD1) have been associated with ALS. Several transgenic murine models exist in which various mutant SOD1s are expressed. We have used differential in-gel electrophoresis (DIGE) to analyze the changes in the spinal cord proteome induced by expression of the unstable SOD1 truncation mutant G127insTGGG (G127X) in mice. Unlike mutants used in most other models, G127X lacks SOD activity and is present at low levels, thus reducing the risk of overexpression artifacts. The mice were analyzed at their peak body weights, just before onset of symptoms. Variable importance plot (VIP) analysis showed that 420 of 1,800 detected protein spots contributed significantly to the differences between the groups. By MALDI-TOF MS analysis, 54 proteins were identified. One spot was found to be a covalently linked mutant SOD1 dimer, apparently analogous to SOD1 immunoreactive bands migrating at double the molecular weight of SOD1 monomers previously detected in humans and mice carrying mutant SOD1s and in sporadic ALS cases. Analyses of affected functional pathways, and the subcellular representation of alterations suggest that the toxicity exerted by mutant SODs induces oxidative stress and affects mitochondria, cellular assembly/organization, and protein degradation.
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| 5. |
- Bergemalm, Daniel, et al.
(författare)
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Superoxide dismutase-1 and other proteins in inclusions from transgenic amyotrophic lateral sclerosis model mice
- 2010
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Ingår i: Journal of Neurochemistry. - : Wiley. - 0022-3042 .- 1471-4159. ; 114:2, s. 408-418
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Tidskriftsartikel (refereegranskat)abstract
- Mutant superoxide dismutase-1 (SOD1) causes amyotrophic lateral sclerosis (ALS) through a cytotoxic mechanism of unknown nature. A hallmark in ALS patients and transgenic mouse models carrying human SOD1 (hSOD1) mutations are hSOD1-immunoreactive inclusions in spinal cord ventral horns. The hSOD1 inclusions may block essential cellular functions or cause toxicity through sequestering of other proteins. Inclusions from four different transgenic mouse models were examined after density gradient ultracentrifugation. The inclusions are complex structures with heterogeneous densities and are disrupted by detergents. The aggregated hSOD1 was mainly composed of subunits that lacked the native stabilizing intra-subunit disulfide bond. A proportion of subunits formed hSOD1 oligomers or was bound to other proteins through disulfide bonds. Dense inclusions could be isolated and the protein composition was analyzed using proteomic techniques. Mutant hSOD1 accounted for half of the protein. Ten other proteins were identified. Two were cytoplasmic chaperones, four were cytoskeletal proteins, and 4 were proteins that normally reside in the endoplasmic reticulum (ER). The presence of ER proteins in inclusions containing the primarily cytosolic hSOD1 further supports the notion that ER stress is involved in ALS.
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| 6. |
- Bergemalm, Daniel, 1977-, et al.
(författare)
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Superoxide dismutase-1 and other proteins in inclusions from transgenic amyotrophic lateral sclerosis model mice
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Mutant superoxide dismutase-1 (SOD1) causes amyotrophic lateral sclerosis (ALS) through a cytotoxic mechanism of unknown nature. A hallmark in ALS patients and transgenic mouse models carrying human SOD1 (hSOD1) mutations are hSOD1-immunoreactive inclusions in spinal cord ventral horns. The hSOD1 inclusions may block essential cellular functions or cause toxicity through sequestering of other proteins. Inclusions from 4 different transgenic mouse models were examined after density gradient ultracentrifugation. The inclusions are complex structures with heterogeneous densities and are disrupted by detergents. The aggregated hSOD1 was mainly composed of subunits that lacked the native stabilizing intrasubunit disulfide bond. A proportion of subunits formed hSOD1 oligomers or was bound to other proteins through disulfide bonds. Dense inclusions could be isolated and the protein composition was analyzed using proteomic techniques. Mutant hSOD1 accounted for half of the protein. Ten other proteins were identified. Two were cytoplasmic chaperones, 4 were cytoskeletal proteins, and 4 were proteins that normally reside in the endoplasmic reticulum (ER). The presence of ER proteins in inclusions containing the primarily cytosolic hSOD1 further supports the notion that ER stress is involved in ALS.
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| 7. |
- Bergström, Tobias, et al.
(författare)
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Developmentally regulated collagen/integrin interactions confer adhesive properties to early postnatal neural stem cells
- 2014
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Ingår i: Biochimica et Biophysica Acta - General Subjects. - : Elsevier BV. - 0304-4165 .- 1872-8006. ; 1840:8, s. 2526-2532
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Tidskriftsartikel (refereegranskat)abstract
- Background:It is becoming increasingly apparent that the extracellular matrix acts as an important regulator of the neural stem niche. Previously we found that neural stem and progenitor cells (NSPCs) derived from the early postnatal subventricular zone of mice adhere to a collagen/hyaluronan hydrogel, whereas NSPCs from the adult and embryonic brain do not.Methods:To examine the specific adhesive properties of young stem cells in more detail, NSPCs isolated from embryonic, postnatal day 6 (P6), and adult mouse brains were cultured on collagen I.Results:Early postnatal NSPCs formed paxillin-positive focal adhesions on collagen I, and these adhesions could be prevented by an antibody that blocked integrin beta 1. Furthermore, we found the corresponding integrin alpha subunits alpha 2 and alpha 11 levels to be highest at the postnatal stage. Gene ontology analysis of differentially expressed genes showed higher expression of transcripts involved in vasculature development and morphogenesis in P6 stem cells, compared to adult.Conclusions:The ability to interact with the extracellular matrix differs between postnatal and adult NSPCs.General significance:Our observations that the specific adhesive properties of early postnatal NSPCs, which are lost in the adult brain, can be ascribed to the integrin subunits expressed by the former furthering our understanding of the developing neurogenic niche. This article is part of a Special Issue entitled Matrix-mediated cell behaviour and properties.
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| 8. |
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| 9. |
- Bivik Stadler, Caroline, 1986-, et al.
(författare)
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Proactive Construction of an Annotated Imaging Database for Artificial Intelligence Training
- 2021
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Ingår i: Journal of digital imaging. - : Springer-Verlag New York. - 0897-1889 .- 1618-727X. ; 34, s. 105-115
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Tidskriftsartikel (refereegranskat)abstract
- Artificial intelligence (AI) holds much promise for enabling highly desired imaging diagnostics improvements. One of the most limiting bottlenecks for the development of useful clinical-grade AI models is the lack of training data. One aspect is the large amount of cases needed and another is the necessity of high-quality ground truth annotation. The aim of the project was to establish and describe the construction of a database with substantial amounts of detail-annotated oncology imaging data from pathology and radiology. A specific objective was to be proactive, that is, to support undefined subsequent AI training across a wide range of tasks, such as detection, quantification, segmentation, and classification, which puts particular focus on the quality and generality of the annotations. The main outcome of this project was the database as such, with a collection of labeled image data from breast, ovary, skin, colon, skeleton, and liver. In addition, this effort also served as an exploration of best practices for further scalability of high-quality image collections, and a main contribution of the study was generic lessons learned regarding how to successfully organize efforts to construct medical imaging databases for AI training, summarized as eight guiding principles covering team, process, and execution aspects.
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| 10. |
- Brännvall, Karin, et al.
(författare)
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Central nervous system stem/progenitor cells form neurons and peripheral glia after transplantation to the dorsal root ganglion.
- 2006
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Ingår i: NeuroReport. - 0959-4965 .- 1473-558X. ; 17:6, s. 623-628
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Tidskriftsartikel (refereegranskat)abstract
- We asked whether neural stem/progenitor cells from the cerebral cortex of E14.5 enhanced green fluorescent protein transgenic mice are able to survive grafting and differentiate in the adult rat dorsal root ganglion. Neurospheres were placed in lumbar dorsal root ganglion cavities after removal of the dorsal root ganglia. Alternatively, dissociated neurospheres were injected into intact dorsal root ganglia. Enhanced green fluorescent protein-positive cells in the dorsal root ganglion cavity were located in clusters and expressed beta-III-tubulin or glial fibrillary acidic protein after 1 month, whereas after 3 months, surviving grafted cells expressed only glial fibrillary acidic protein. In the intact adult DRG, transplanted neural stem/progenitor cells surrounded dorsal root ganglion cells and fibers, and expressed glial but not neuronal markers. These findings show that central nervous system stem/progenitor cells can survive and differentiate into neurons and peripheral glia after xenotransplantation to the adult dorsal root ganglion.
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| 11. |
- Brännvall, Karin, et al.
(författare)
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Enhanced neuronal differentiation in a three-dimensional collagen-hyaluronan matrix
- 2007
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Ingår i: Journal of Neuroscience Research. - : Wiley. - 0360-4012 .- 1097-4547. ; 85:10, s. 2138-2146
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Tidskriftsartikel (refereegranskat)abstract
- Efficient 3D cell systems for neuronal induction are needed for future use in tissue regeneration. In this study, we have characterized the ability of neural stem/progenitor cells (NS/PC) to survive, proliferate, and differentiate in a collagen type I-hyaluronan scaffold. Embryonic, postnatal, and adult NS/PC were seeded in the present 3D scaffold and cultured in medium containing epidermal growth factor and fibroblast growth factor-2, a condition that stimulates NS/PC proliferation. Progenitor cells from the embryonic brain had the highest proliferation rate, and adult cells the lowest, indicating a difference in mitogenic responsiveness. NS/PC from postnatal stages down-regulated nestin expression more rapidly than both embryonic and adult NS/PC, indicating a faster differentiation process. After 6 days of differentiation in the 3D scaffold, NS/PC from the postnatal brain had generated up to 70% neurons, compared with 14% in 2D. NS/PC from other ages gave rise to approximately the same proportion of neurons in 3D as in 2D (9-26% depending on the source for NS/PC). In the postnatal NS/PC cultures, the majority of III-tubulin-positive cells expressed glutamate, -aminobutyric acid, and synapsin I after 11 days of differentiation, indicating differentiation to mature neurons. Here we report that postnatal NS/PC survive, proliferate, and efficiently form synapsin I-positive neurons in a biocompatible hydrogel.
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| 12. |
- Brännvall, Karin, et al.
(författare)
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Environmental cues from CNS, PNS, and ENS cells regulate CNS progenitor differentiation
- 2008
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Ingår i: NeuroReport. - 0959-4965 .- 1473-558X. ; 19:13, s. 1283-9
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Tidskriftsartikel (refereegranskat)abstract
- Cellular origin and environmental cues regulate stem cell fate determination. Neuroepithelial stem cells form the central nervous system (CNS), whereas neural crest stem cells generate the peripheral (PNS) and enteric nervous system (ENS). CNS neural stem/progenitor cell (NSPC) fate determination was investigated in combination with dissociated cultures or conditioned media from CNS, PNS, or ENS. Cells or media from ENS or PNS cultures efficiently promoted NSPC differentiation into neurons, glia, and smooth muscle cells with a similar morphology as the feeder culture. Together with CNS cells or its conditioned medium, NSPC differentiation was partly inhibited and cells remained immature. Here, we demonstrate that secreted factors from the environment can influence CNS progenitor cells to choose a PNS-like cell fate.
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| 13. |
- Ekenberg, Love, et al.
(författare)
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Deliberation, representation, equity : research approaches, tools and algorithms for participatory processes
- 2017
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Bok (övrigt vetenskapligt/konstnärligt)abstract
- What can we learn about the development of public interaction in e-democracy from a drama delivered by mobile headphones to an audience standing around a shopping center in a Stockholm suburb? In democratic societies there is widespread acknowledgment of the need to incorporate citizens' input in decision-making processes in more or less structured ways. But participatory decision making is balancing on the borders of inclusion, structure, precision and accuracy. To simply enable more participation will not yield enhanced democracy, and there is a clear need for more elaborated elicitation and decision analytical tools. This rigorous and thought-provoking volume draws on a stimulating variety of international case studies, from flood risk management in the Red River Delta of Vietnam, to the consideration of alternatives to gold mining in Ro?ia Montana in Transylvania, to the application of multi-criteria decision analysis in evaluating the impact of e-learning opportunities at Uganda's Makerere University. Editors Love Ekenberg (senior research scholar, International Institute for Applied Systems Analysis [IIASA], Laxenburg, professor of Computer and Systems Sciences, Stockholm University), Karin Hansson (artist and research fellow, Department of Computer and Systems Sciences, Stockholm University), Mats Danielson (vice president and professor of Computer and Systems Sciences, Stockholm University, affiliate researcher, IIASA) and Göran Cars (professor of Societal Planning and Environment, Royal Institute of Technology, Stockholm) draw innovative collaborations between mathematics, social science, and the arts. They develop new problem formulations and solutions, with the aim of carrying decisions from agenda setting and problem awareness through to feasible courses of action by setting objectives, alternative generation, consequence assessments, and trade-off clarifications. As a result, this book is important new reading for decision makers in government, public administration and urban planning, as well as students and researchers in the fields of participatory democracy, urban planning, social policy, communication design, participatory art, decision theory, risk analysis and computer and systems sciences.
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| 14. |
- Erlandsson, Anna, et al.
(författare)
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Autocrine/Paracrine platelet-derived growth factor regulates proliferation of neural progenitor cells
- 2006
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Ingår i: Cancer Research. - 0008-5472 .- 1538-7445. ; 66:16, s. 8042-8048
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Tidskriftsartikel (refereegranskat)abstract
- Growth factors play an important role in regulating neural stem cell proliferation and differentiation. This study shows that platelet-derived growth factor (PDGF) induces a partial differentiation of neural stem/progenitor cells (NSPCs) in the absence of other mitogens in vitro. NSPCs thus acquire an immature morphology and display markers for both neurons and glia. In addition, these cells do not readily mature in the absence of further stimuli. When NSPC cultures treated with PDGF were exposed to additional differentiation factors, however, the differentiation proceeded into neurons, astrocytes, and oligodendrocytes. We find that NSPC cultures are endowed with an endogenous PDGF-BB production. The PDGF-BB expression peaks during early differentiation and is present both in cell lysates and in conditioned medium, allowing for autocrine as well as paracrine signaling. When the NSPC-derived PDGF was inhibited, progenitor cell numbers decreased, showing that PDGF is involved in NSPC expansion. Addition of a PDGF receptor (PDGFR) inhibitor resulted in a more rapid differentiation. Neurons and oligodendrocytes appeared earlier and had more elaborate processes than in control cultures where endogenous PDGFR signaling was not blocked. Our observations point to PDGF as an inducer of partial differentiation of NSPC that also sustains progenitor cell division. Such an intermediate stage in stem cell differentiation is of relevance for the understanding of brain tumor development because autocrine PDGF stimulation is believed to drive malignant conversion of central nervous system progenitor cells.
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| 15. |
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| 16. |
- Forsberg, Karin, et al.
(författare)
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Misfolded SOD1 inclusions in patients with mutations in C9orf72 and other ALS/FTD-associated genes
- 2019
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Ingår i: Journal of Neurology, Neurosurgery and Psychiatry. - : BMJ Publishing Group Ltd. - 0022-3050 .- 1468-330X. ; 90:8, s. 861-869
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Tidskriftsartikel (refereegranskat)abstract
- Objective: A hallmark of amyotrophic lateral sclerosis (ALS) caused by mutations in superoxide dismutase-1 (SOD1) are inclusions containing SOD1 in motor neurons. Here, we searched for SOD1-positive inclusions in 29 patients carrying ALS-linked mutations in six other genes.Methods: A panel of antibodies that specifically recognise misfolded SOD1 species were used for immunohistochemical investigations of autopsy tissue.Results: The 18 patients with hexanucleotide-repeat-expansions in C9orf72 had inclusions of misfolded wild type (WT) SOD1(WT) in spinal motor neurons. Similar inclusions were occasionally observed in medulla oblongata and in the motor cortex and frontal lobe. Patients with mutations in FUS, KIF5A, NEK1, ALSIN or VAPB, carried similar SOD1(WT) inclusions. Minute amounts of misSOD1(WT) inclusions were detected in 2 of 20 patients deceased from non-neurological causes and in 4 of 10 patients with other neurodegenerative diseases. Comparison was made with 17 patients with 9 different SOD1 mutations. Morphologically, the inclusions in patients with mutations in C9orf72HRE, FUS, KIF5A, NEK1, VAPB and ALSIN resembled inclusions in patients carrying the wildtype-like SOD1(D90A) mutation, whereas patients carrying unstable SOD1 mutations (A4V, V5M, D76Y, D83G, D101G, G114A, G127X, L144F) had larger skein-like SOD1-positive inclusions.Conclusions and relevance Abundant inclusions containing misfolded SOD1(WT) are found in spinal and cortical motor neurons in patients carrying mutations in six ALS-causing genes other than SOD1. This suggests that misfolding of SOD1(WT) can be part of a common downstream event that may be pathogenic. The new anti-SOD1 therapeutics in development may have applications for a broader range of patients.
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| 17. |
- Forsberg, Karin, et al.
(författare)
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Novel antibodies reveal inclusions containing non-native SOD1 in sporadic ALS patients
- 2010
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Ingår i: PLOS ONE. - : Public library of science. - 1932-6203. ; 5:7, s. e11552-
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Tidskriftsartikel (refereegranskat)abstract
- Mutations in CuZn-superoxide dismutase (SOD1) cause amyotrophic lateral sclerosis (ALS) and are found in 6% of ALS patients. Non-native and aggregation-prone forms of mutant SOD1s are thought to trigger the disease. Two sets of novel antibodies, raised in rabbits and chicken, against peptides spaced along the human SOD1 sequence, were by enzyme-linked immunosorbent assay and an immunocapture method shown to be specific for denatured SOD1. These were used to examine SOD1 in spinal cords of ALS patients lacking mutations in the enzyme. Small granular SOD1-immunoreactive inclusions were found in spinal motoneurons of all 37 sporadic and familial ALS patients studied, but only sparsely in 3 of 28 neurodegenerative and 2 of 19 non-neurological control patients. The granular inclusions were by confocal microscopy found to partly colocalize with markers for lysosomes but not with inclusions containing TAR DNA binding protein-43, ubiquitin or markers for endoplasmic reticulum, autophagosomes or mitochondria. Granular inclusions were also found in carriers of SOD1 mutations and in spinobulbar muscular atrophy (SBMA) patients and they were the major type of inclusion detected in ALS patients homozygous for the wild type-like D90A mutation. The findings suggest that SOD1 may be involved in ALS pathogenesis in patients lacking mutations in the enzyme.
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| 18. |
- Forsberg, Karin, et al.
(författare)
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Widespread CNS pathology in amyotrophic lateral sclerosis homozygous for the D90A SOD1 mutation
- 2023
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Ingår i: Acta Neuropathologica. - : Springer-Verlag New York. - 0001-6322 .- 1432-0533. ; 145:1, s. 13-28
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Tidskriftsartikel (refereegranskat)abstract
- Mutations in the gene encoding the ubiquitously expressed free radical scavenging enzyme superoxide dismutase-1 (SOD1) are found in 2–6% of amyotrophic lateral sclerosis patients. The most frequent SOD1 mutation worldwide is D90A. Amyotrophic lateral sclerosis caused by this mutation has some unusual features: the heredity is usually recessive, the phenotype is stereotypic with slowly evolving motor symptoms beginning in the legs and may also include sensory, autonomic, and urinary bladder involvement. Furthermore, the mutant protein resembles the wild type, with normal content and enzymatic activity in the central nervous system. Here, we report neuropathological findings in nine patients homozygous for the D90A mutation. All nine had numerous small granular inclusions immunoreactive for misfolded SOD1 in motor neurons and glial nuclei in the spinal cord and brainstem. In addition to degeneration of the corticospinal tracts, all patients had degeneration of the dorsal columns. We also found intense gliosis in circumscribed cortical areas of the frontal and temporal lobes and in the insula. In these areas and in adjacent white matter, there were SOD1 staining neuropil threads. A few SOD1-immunopositive cytoplasmic neuronal inclusions were observed in cortical areas, as were glial nuclear inclusions. As suggested by the symptoms and signs and earlier neurophysiological and imaging investigations, the histopathology in patients homozygous for the D90A SOD1 extends beyond the motor system to include cognitive and sensory cortical areas. However, even in the patients that had a symptomatic disease duration of more than 2 or 3 decades and lived into their 70s or 80s, there were no SOD1-inclusion pathology and no typical dysfunction (apart from the musculature) in non-nervous organs. Thus, only specific parts of the CNS seem to be vulnerable to toxicity provoked by homozygously expressed mutant SOD1.
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| 19. |
- Forsberg, Maud, et al.
(författare)
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Undersulfation of Heparan Sulfate Restricts Differentiation Potential of Mouse Embryonic Stem Cells
- 2012
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 287:14, s. 10853-10862
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Tidskriftsartikel (refereegranskat)abstract
- Heparan sulfate proteoglycans, present on cell surfaces and in the extracellular matrix, interact with growth factors and morphogens to influence growth and differentiation of cells. The sulfation pattern of the heparan sulfate chains formed during biosynthesis in the Golgi compartment will determine the interaction potential of the proteoglycan. The glucosaminyl N-deacetylase/N-sulfotransferase (NDST) enzymes have a key role during biosynthesis, greatly influencing total sulfation of the heparan sulfate chains. The differentiation potential of mouse embryonic stem cells lacking both NDST1 and NDST2 was studied using in vitro differentiation protocols, expression of differentiation markers, and assessment of the ability of the cells to respond to growth factors. The results show that NDST1 and NDST2 are dispensable for mesodermal differentiation into osteoblasts but necessary for induction of adipocytes and neural cells. Gene expression analysis suggested a differentiation block at the primitive ectoderm stage. Also, GATA4, a primitive endoderm marker, was expressed by these cells. The addition of FGF4 or FGF2 together with heparin rescued the differentiation potential to neural progenitors and further to mature neurons and glia. Our results suggest that the embryonic stem cells lacking both NDST1 and NDST2, expressing a very low sulfated heparan sulfate, can take the initial step toward differentiation into all three germ layers. Except for their potential for mesodermal differentiation into osteoblasts, the cells are then arrested in a primitive ectoderm and/or endoderm stage.
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| 20. |
- Fromell, Karin, et al.
(författare)
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Designed protein binders in combination with nanocrystalline diamond for use in high-sensitivity biosensors
- 2012
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Ingår i: Analytical and Bioanalytical Chemistry. - : Springer Science and Business Media LLC. - 1618-2642 .- 1618-2650. ; 404:6-7, s. 1643-1651
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Tidskriftsartikel (refereegranskat)abstract
- A platform for diagnostic applications showing signal-to-noise ratios that by far surpass those of traditional bioanalytical test formats has been developed. It combines the properties of modified nanocrystalline diamond (NCD) surfaces and those of polyethylene oxide and polypropylene oxide based block copolymers for surface passivation and binder conjugation with a new class of synthetic binders for proteins. The NCD surfaces were fluorine-, hydrogen-, or oxygen-terminated prior to further biofunctionalization and the surface composition was characterized by X-ray photoelectron spectroscopy. In a proof of principle demonstration targeting the C-reactive protein, an ELISA carried out using an F-terminated diamond surface showed a signal-to-noise ratio of 3,900 which compares well to the signal-to-noise of 89 obtained in an antibody-based ELISA on a polystyrene microtiter plate, a standard test format used in most life science laboratories today. The increase in signal-to-noise ratio is to a large extent the result of extremely efficient passivation of the diamond surface. The results suggest that significant improvements can be obtained in standardized test formats using new materials in combination with new types of chemical coatings and receptor molecules.
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| 21. |
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| 22. |
- Graffmo, Karin S., et al.
(författare)
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Expression of wild-type human superoxide dismutase-1 in mice causes amyotrophic lateral sclerosis
- 2013
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 22:1, s. 51-60
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Tidskriftsartikel (refereegranskat)abstract
- A common cause of amyotrophic lateral sclerosis (ALS) is mutations in the gene encoding superoxide dismutase-1. There is evolving circumstantial evidence that the wild-type protein can also be neurotoxic and that it may more generally be involved in the pathogenesis of ALS. To test this proposition more directly, we generated mice that express wild-type human superoxide dismutase-1 at a rate close to that of mutant superoxide dismutase-1 in the commonly studied G93A transgenic model. These mice developed an ALS-like syndrome and became terminally ill after around 370 days. The loss of spinal ventral neurons was similar to that in the G93A and other mutant superoxide dismutase-1 models, and large amounts of aggregated superoxide dismutase-1 were found in spinal cords, but also in the brain. The findings show that wild-type human superoxide dismutase-1 has the ability to cause ALS in mice, and they support the hypothesis of a more general involvement of the protein in the disease in humans.
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| 23. |
- Hedlund, Gunnar, et al.
(författare)
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The Tumor Targeted Superantigen ABR-217620 Selectively Engages TRBV7-9 and Exploits TCR-pMHC Affinity Mimicry in Mediating T Cell Cytotoxicity.
- 2013
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:10
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Tidskriftsartikel (refereegranskat)abstract
- The T lymphocytes are the most important effector cells in immunotherapy of cancer. The conceptual objective for developing the tumor targeted superantigen (TTS) ABR-217620 (naptumomab estafenatox, 5T4Fab-SEA/E-120), now in phase 3 studies for advanced renal cell cancer, was to selectively coat tumor cells with cytotoxic T lymphocytes (CTL) target structures functionally similar to natural CTL pMHC target molecules. Here we present data showing that the molecular basis for the anti-tumor activity by ABR-217620 resides in the distinct interaction between the T cell receptor β variable (TRBV) 7-9 and the engineered superantigen (Sag) SEA/E-120 in the fusion protein bound to the 5T4 antigen on tumor cells. Multimeric but not monomeric ABR-217620 selectively stains TRBV7-9 expressing T lymphocytes from human peripheral blood similar to antigen specific staining of T cells with pMHC tetramers. SEA/E-120 selectively activates TRBV7-9 expressing T lymphocytes resulting in expansion of the subset. ABR-217620 selectively triggers TRBV7-9 expressing cytotoxic T lymphocytes to kill 5T4 positive tumor cells. Furthermore, ABR-217620 activates TRBV7-9 expressing T cell line cells in the presence of cell- and bead-bound 5T4 tumor antigen. Surface plasmon resonance analysis revealed that ABR-217620 binds to 5T4 with high affinity, to TRBV7-9 with low affinity and to MHC class II with very low affinity. The T lymphocyte engagement by ABR-217620 is constituted by displaying high affinity binding to the tumor cells (KD approximately 1 nM) and with the mimicry of natural productive immune TCR-pMHC contact using affinities of around 1 µM. This difference in kinetics between the two components of the ABR-217620 fusion protein will bias the binding towards the 5T4 target antigen, efficiently activating T-cells via SEA/E-120 only when presented by the tumor cells.
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| 24. |
- Kriz, Vitezslav, et al.
(författare)
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Shb null allele is inherited with a transmission ratio distortion and causes reduced viability in utero
- 2007
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Ingår i: Developmental Dynamics. - : Wiley. - 1058-8388 .- 1097-0177. ; 236:9, s. 2485-2492
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Tidskriftsartikel (refereegranskat)abstract
- SHB is an Src homology 2 domain-containing adapter protein that has been found to be involved in numerous cellular responses. We have generated an Shb knockout mouse. No Shb-/- pups or embryos were obtained on the C57Bl6 background, indicating an early defect as a consequence of Shb- gene inactivation on this genetic background. Breeding heterozygotes for Shb gene inactivation (Shb+/-) on a mixed genetic background (FVB/C57Bl6/129Sv) reveals a distorted transmission ratio of the null allele with reduced numbers of Shb+/+ and Shb-/- animals, but increased number of Shb+/- animals. The Shb- allele is associated with various forms of malformations, explaining the relative reduction in the number of Shb-/- offspring. Shb-/- animals that were born were viable, fertile, and showed no obvious defects. However, Shb+/- female mice ovulated preferentially Shb- oocytes explaining the reduced frequency of Shb+/+ mice. Our study suggests a role of SHB during reproduction and development.
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| 25. |
- Looman, Camilla, et al.
(författare)
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An activating mutation in the PDGF receptor-beta causes abnormal morphology in the mouse placenta
- 2007
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Ingår i: International Journal of Developmental Biology. - : UPV/EHU Press. - 0214-6282 .- 1696-3547. ; 51:5, s. 361-370
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Tidskriftsartikel (refereegranskat)abstract
- An oncogenic D842V mutation in the platelet-derived growth factor (PDGF) alpha-receptor (Pdgfra) has recently been described in patients with gastrointestinal stromal tumors. In order to test if the same mutation would confer oncogenic properties to the homologous PDGF beta-receptor (Pdgfrb), the corresponding aspartic acid residue at position 849 of Pdgfrb was changed into valine (D849V) using a knock-in strategy. This mutation turned out to be dominantly lethal and caused death even in chimeras (from 345 transferred chimeric blastocysts, no living coat chimeras were detected). Experiments employing mouse embryonic fibroblasts (MEFs) indicated hyperactivity of the mutant receptor. The mutant receptor was phosphorylated in a ligand-independent manner and, in contrast to wild-type MEFs, mutant cells proliferated even in the absence of ligand. Knockout experiments have previously indicated a role for Pdgfrb in placental development. We therefore analyzed wild-type and Pdgfrb D849V chimeric placentas from different gestational stages. No differences were detected at embryonic days 11.5 and 13.5 (n=4). At embryonic day 17.5, however, chimeric placentas (n=3/4) displayed abnormalities both in the labyrinth and in the chorionic plate. The changes included hyper-proliferation of alpha-smooth muscle actin and platelet/endothelial cell adhesion molecule-1 positive cells in the labyrinth and cells in the chorionic plate. In addition, the fetal blood vessel compartment of the labyrinth was completely disorganized.
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| 26. |
- Moberg, Christina, et al.
(författare)
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De unga gör helt rätt när de stämmer staten
- 2022
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Ingår i: Aftonbladet. - 1103-9000.
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- 1 620 forskare och lärare i forskarvärlden: Vi ställer oss bakom Auroras klimatkrav
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| 27. |
- Niklasson, Mia, et al.
(författare)
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Enlarged lateral ventricles and aberrant behavior in mice overexpressing PDGF-B in embryonic neural stem cells
- 2010
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Ingår i: Experimental Cell Research. - : Elsevier BV. - 0014-4827 .- 1090-2422. ; 316:17, s. 2779-2789
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Tidskriftsartikel (refereegranskat)abstract
- Platelet-derived growth factor (PDGF) is important in central nervous system (CNS) development, and aberrant expression of PDGF and its receptors has been linked to developmental defects and brain tumorigenesis. We previously found that neural stem and progenitor cells in culture produce PDGF and respond to it by autocrine and/or paracrine signaling. We therefore aimed to examine CNS development after PDGF overexpression in neural stem cells in vivo. Transgenic mice were generated with PDGF-B under control of a minimal nestin enhancer element, which is specific for embryonic expression and will not drive adult expression in mice. The resulting mouse showed increased apoptosis in the developing striatum, which suggests a disturbed regulation of progenitor cells. Later in neurodevelopment, in early postnatal life, mice displayed enlarged lateral ventricles. This enlargement remained into adulthood and it was more pronounced in male mice than in transgenic female mice. Nevertheless, there was an overall normal composition of cell types and numbers in the brain and the transgenic mice were viable and fertile. Adult transgenic males, however, showed behavioral aberrations and locomotor dysfunction. Thus, a tightly regulated expression of PDGF during embryogenesis is required for normal brain development and function in mice.
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| 28. |
- Nordin, Angelica, et al.
(författare)
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Extensive size variability of the GGGGCC expansion in C9orf72 in both neuronal and non-neuronal tissues in 18 patients with ALS or FTD
- 2015
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 24:11, s. 3133-3142
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Tidskriftsartikel (refereegranskat)abstract
- A GGGGCC-repeat expansion in C9orf72 is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) among Caucasians. However, little is known about the variability of the GGGGCC expansion in different tissues and whether this correlates with the observed phenotype. Here, we used Southern blotting to estimate the size of hexanucleotide expansions in C9orf72 in neural and non-neural tissues from 18 autopsied ALS and FTD patients with repeat expansion in blood. Digitalization of the Southern blot images allowed comparison of repeat number, smear distribution and expansion band intensity between tissues and between patients. We found marked intra-individual variation of repeat number between tissues, whereas there was less variation within each tissue group. In two patients, the size variation between tissues was extreme, with repeat numbers below 100 in all studied non-neural tissues, whereas expansions in neural tissues were 20-40 times greater and in the same size range observed in neural tissues of the other 16 patients. The expansion pattern in different tissues could not distinguish between diagnostic groups and no correlation was found between expansion size in frontal lobe and occurrence of cognitive impairment. In ALS patients, a less number of repeats in the cerebellum and parietal lobe correlated with earlier age of onset and a larger number of repeats in the parietal lobe correlated with a more rapid progression. In 43 other individuals without repeat expansion in blood, we find that repeat sizes up to 15 are stable, as no size variation between blood, brain and spinal cord was found.
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| 29. |
- Ossipov, Dmitri, et al.
(författare)
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Formation of the first injectable poly(vinyl alcohol) hydrogel by mixing of functional PVA precursors
- 2007
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Ingår i: Journal of Applied Polymer Science. - : Wiley. - 0021-8995 .- 1097-4628. ; 106:1, s. 60-70
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Tidskriftsartikel (refereegranskat)abstract
- In this study we describe the development of an injectable, in situ chemical hydrogel forming system. The gelation occurs under neutral pH and at room temperature immediately upon mixing of the two aqueous poly (vinyl alcohol) components specifically derivatized through carbamate linkages with aldehyde (PVA-AL) and hydrazide (PVA-HY) functional groups, respectively. Aldehyde and hydrazide pendant groups were incorporated with a low degree of substitution (DS) into the PVA backbone to keep PVA structural homogeneity minimally altered. As a result, the hydrazone crosslinks are formed rapidly between aldehyde and hydrazide pendant groups when the correspondingly modified PVA components are brought in contact as water solutions. To assess in situ hydrazone crosslinks formation for in vitro cytocompatibility, murine neuroblastoma N2a cells were suspended in cell culture medium with the dissolved PVA-HY prior to addition to the PVA-AL aqueous solution. Thus, the cells were chemically encapsulated in a polymer network that was formed by mixing of the corresponding aqueous solutions of PVA functional precursors. Biochemical analysis revealed that cells survived chemical crosslinking and remained viable in the hydrogel for 4 days of culture.
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| 30. |
- Stubberud, Karin, et al.
(författare)
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Partial filling micellar electrokinetic chromatography optimisation studies of ibuprofen, codeine and degradation products, and coupling to mass spectrometry : Part I
- 2002
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Ingår i: Electrophoresis. - 0173-0835 .- 1522-2683. ; 23:4, s. 572-577
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Tidskriftsartikel (refereegranskat)abstract
- Studies have been performed to evaluate whether an on-line partial filling-micellar electrokinetic chromatography (PF-MEKC) system could be applied to a recently developed MEKC method for the separation of ibuprofen, codeine and one of the degradation products. Attempts to couple the PF-MEKC system to MS have also been performed. SDS concentration, micellar zone length and concentration of acetonitrile in the buffer were optimized using factorial design. When a small micelle zone was injected directly after the sample introduction, the results improved markedly. The MS parameters have not been optimized, but the studies show promising results for the use of PF-MEKC-mass spectrometry for identification of the degradation products.
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| 31. |
- Wallenquist, Ulrika, 1975-, et al.
(författare)
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Grafted neural progenitors migrate and form neurons after experimental traumatic brain injury
- 2009
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Ingår i: Restorative Neurology and Neuroscience. - Amsterdam : IOS Press. - 0922-6028 .- 1878-3627. ; 27:4, s. 323-334
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSENeural stem and progenitor cells (NSPC) generate neurons and glia, a feature that makes them attractive for cell replacement therapies. However, efforts to transplant neural progenitors in animal models of brain injury typically result in high cell mortality and poor neuronal differentiation.METHODSIn an attempt to improve the outcome for grafted NSPC after controlled cortical impact we transplanted Enhanced Green Fluorescent Protein (EGFP)-positive NSPC into the contra lateral ventricle of mice one week after injury.RESULTSGrafted EGFP-NSPC readily migrated to the injured hemisphere where we analyzed the proportion of progenitors and differentiated progeny at different time points. Transplantation directly into the injured parenchyma, resulted in few brains with detectable EGFP-NSPC. On the contrary, in more than 90% of the mice that received a transplant into the lateral ventricle detectable EGFP-positive cells were found. The cells were integrated into the lateral ventricle wall of the un-injured hemisphere, throughout the corpus callosum, and in the cortical perilesional area. At one-week post transplantation, grafted cells that had migrated to the perilesion area mainly expressed markers of neural progenitors and neurons, while in the corpus callosum and the ventricular lining, grafted cells with a glial fate were more abundant. After 3 months, grafted cells in the perilesion area were less abundant whereas cells that had migrated to the walls of the third- and lateral- ventricle of the injured hemisphere were still detectable, suggesting that the injury site remained a hostile environment.CONCLUSIONTransplantation to the lateral ventricle, presumably for being a neurogenic region, provides a favorable environment improving the outcome for grafted NSPC both in term of their appearance at the cortical site of injury, and their acquisition of neural markers.
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| 32. |
- Wallenquist, Ulrika, et al.
(författare)
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Ibuprofen attenuates the inflammatory response and allows formation of migratory neuroblasts from grafted stem cells after traumatic brain injury
- 2012
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Ingår i: Restorative Neurology and Neuroscience. - 0922-6028 .- 1878-3627. ; 30:1, s. 9-19
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: There is hope for neural stem and progenitor cells (NSPC) to enhance regeneration when transplanted to the injured brain after traumatic brain injury (TBI). So far, the therapeutic effects of NSPC transplantation have been hampered mainly by the notable death of the transplanted cells. Neuroinflammation may lead to additional cell death after TBI and we hypothesized that survival of grafted NSPC could be enhanced by anti-inflammatory treatment. Methods: Mice that were subjected to controlled cortical impact TBI and grafted with NSPC, were treated with the non-steroidal anti-inflammatory drug ibuprofen. Results: Ibuprofen was found to down-regulate the TBI-induced inflammatory response. In addition, migrating neuroblasts from transplanted cells were observed near the contusion and in the ipsilateral hippocampus in ibuprofen-treated animals only, suggesting that the anti-inflammatory treatment had beneficial effects on graft survival and/or differentiation. However, Morris Water Maze performance or TBI-induced tissue loss was not influenced by ibuprofen treatment. Conclusions: Our data suggests that anti-inflammatory strategies may be a complement to enhance the outcome for the cell transplants following TBI.
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| 33. |
- Wallenquist, Ulrika, 1975-
(författare)
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Neural Stem and Progenitor Cells as a Tool for Tissue Regeneration
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Neural stem and progenitor cells (NSPC) can differentiate to neurons and glial cells. NSPC are easily propagated in vitro and are therefore an attractive tool for tissue regeneration. Traumatic brain injury (TBI) is a common cause for death and disabilities. A fundamental problem following TBI is tissue loss. Animal studies aiming at cell replacement have encountered difficulties in achieving sufficient graft survival and differentiation. To improve outcome of grafted cells after experimental TBI (controlled cortical impact, CCI) in mice, we compared two transplantation settings. NSPC were transplanted either directly upon CCI to the injured parenchyma, or one week after injury to the contralateral ventricle. Enhanced survival of transplanted cells and differentiation were seen when cells were deposited in the ventricle. To further enhance cell survival, efforts were made to reduce the inflammatory response to TBI by administration of ibuprofen to mice that had been subjected to CCI. Inflammation was reduced, as monitored by a decrease in inflammatory markers. Cell survival as well as differentiation to early neuroblasts seemed to be improved. To device a 3D system for future transplantation studies, NSPC from different ages were cultured in a hydrogel consisting of hyaluronan and collagen. Cells survived and proliferated in this culturing condition and the greatest neuronal differentiating ability was seen in cells from the newborn mouse brain. NSPC were also used in a model of peripheral nervous system injury, and xeno-transplanted to rats where the dorsal root ganglion had been removed. Cells survived and differentiated to neurons and glia, furthermore demonstrating their usefulness as a tool for tissue regeneration.
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| 34. |
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| 35. |
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| 36. |
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| 37. |
- Xiong, Anqi, 1986-, et al.
(författare)
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Heparanase confers a growth advantage to differentiating murine embryonic stem cells, and enhances oligodendrocyte formation.
- 2017
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Ingår i: Matrix Biology. - : Elsevier BV. - 0945-053X .- 1569-1802. ; 62, s. 92-104
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Tidskriftsartikel (refereegranskat)abstract
- Heparan sulfate proteoglycans (HSPGs), ubiquitous components of mammalian cells, play important roles in development and homeostasis. These molecules are located primarily on the cell surface and in the pericellular matrix, where they interact with a multitude of macromolecules, including many growth factors. Manipulation of the enzymes involved in biosynthesis and modification of HSPG structures alters the properties of stem cells. Here, we focus on the involvement of heparanase (HPSE), the sole endo-glucuronidase capable of cleaving of HS, in differentiation of embryonic stem cells into the cells of the neural lineage. Embryonic stem (ES) cells overexpressing HPSE (Hpse-Tg) proliferated more rapidly than WT ES cells in culture and formed larger teratomas in vivo. In addition, differentiating Hpse-Tg ES cells also had a higher growth rate, and overexpression of HPSE in NSPCs enhanced Erk and Akt phosphorylation. Employing a two-step, monolayer differentiation, we observed an increase in HPSE as wild-type (WT) ES cells differentiated into neural stem and progenitor cells followed by down-regulation of HPSE as these NSPCs differentiated into mature cells of the neural lineage. Furthermore, NSPCs overexpressing HPSE gave rise to more oligodendrocytes than WT cultures, with a concomitant reduction in the number of neurons. Our present findings emphasize the importance of HS, in neural differentiation and suggest that by regulating the availability of growth factors and, or other macromolecules, HPSE promotes differentiation into oligodendrocytes.
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| 38. |
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| 39. |
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| 40. |
- Agreus, Lars, et al.
(författare)
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Towards a healthy stomach? : Helicobacter pylori prevalence has dramatically decreased over 23 years in adults in a Swedish community
- 2016
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Ingår i: United European Gastroenterology journal. - : Wiley. - 2050-6406 .- 2050-6414. ; 4:5, s. 686-696
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Tidskriftsartikel (refereegranskat)abstract
- Background In Western countries the prevalence of Helicobacter pylori (H. pylori) infection may be declining but there is a lack of recent longitudinal population studies. We evaluated the changing epidemiology over a 23-year period in Sweden.Materials and methods In 1989, the validated Abdominal Symptom Questionnaire (ASQ) was mailed to a random sample of inhabitants (ages 22-80 years) in a Swedish community, and 1097 (87%) responded. H. pylori serology was analysed in a representative subsample (n=145). Twenty-three years later, the ASQ was mailed again using similar selection criteria, and 388 out of 1036 responders had an upper endoscopy with assessment of H. pylori and corpus atrophy status.Results The prevalence of positive H. pylori serology decreased from 37.9% (1989) to 15.8% (2012), corresponding to a decrease in odds of 75% per decade (odds ratio (OR): 0.25; 95% confidence interval (CI): 0.11-0.59, p=0.001) independent of age, gender, body mass index (BMI) and level of education, with a pattern consistent with a birth cohort effect. The prevalence increased with increasing age (p=0.001). The prevalence of H. pylori on histology in 2012 was 11.4% (95% CI 8.6-15.0). The prevalence of corpus atrophy on serology and/or histology in 2012 was 3.2% (95% CI 1.8-5.5); all cases were 57 years old.Conclusion The stomach is healthier in 2012 compared with 1989. H. pylori prevalence in adults has decreased over the last two decades to a level where clinical management might be affected.
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| 41. |
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| 42. |
- Akselsson, Cecilia, et al.
(författare)
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Samordnad landskapsförvaltning : Ett nytt sätt att förvalta landskap för att uppnå hållbarhetsmålen
- 2020
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Ingår i: ; 6
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Annan publikation (populärvet., debatt m.m.)abstract
- Trycket på både skogs- och jordbruksmark ökar, bland annat som en följd av befolknings-ökningen, ändrade konsumtionsmönster och den pågående klimatförändringen. Detta leder till målkonflikter, där aktörer med olika intressen har olika syn på hur marken ska användas på bästa sätt. Dagens sektorsvisa planering, där beslut ofta tas på fastighetsnivå, gör det svårt att hitta lösningar på dessa målkonflikter. En övergång till en mer samordnad landskapsförvaltning har stor potential, men innebär också att en rad hinder först måste övervinnas.
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| 43. |
- Almung, Magnus, et al.
(författare)
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I solitärens skugga : Nyttobyggnadens kreativa restaurering
- 2015
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Rapport (populärvet., debatt m.m.)abstract
- Ekonomibyggnader har alltid behövts för de huvudbyggnader som finns inom våra bevarade kulturmiljöer. Några nyttobyggnader uppskattas och används fortfarande, andra betraktas som problematiska överloppsbyggnader, många rivs. Alltför få har dokumenterats eller fått sin historia klarlagd vilket undanhållit viktig kunskap om samhällets framväxt. Vi vill synliggöra och betona vikten av att bevara och utveckla hela bebyggelsemiljöer, ofta med ett antal hus utöver huvudbyggnaden och tillhörande yttre miljö i staden eller på landet. Denna rapport visar kursdeltagarnas projektarbeten om nyttobyggnader. De har dokumenterat med traditionella och nya arbetsmetoder, inventerat och intervjuat, läst och besökt arkiv, värderat, analyserat och därefter föreslagit hur man ska ta hand om och utveckla nyttobyggnaderna i sina kulturmiljöer.
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| 44. |
- Anna Karin, Hedström, et al.
(författare)
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The impact of bariatric surgery on disease activity and progression of multiple sclerosis : A nationwide matched cohort study
- 2022
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Ingår i: Multiple Sclerosis Journal. - : Sage Publications. - 1352-4585 .- 1477-0970. ; 28:13, s. 2099-2105
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Surgical outcomes in patients with multiple sclerosis (MS) following metabolic surgery appear to be similar compared to those of the general bariatric population.OBJECTIVE: To study the impact of metabolic surgery on the clinical course of MS.METHODS: Using data from the Scandinavian Obesity Surgery Registry and the Swedish Multiple Sclerosis register, we compared disease outcomes in 122 cases of MS who had undergone metabolic surgery with those of 122 cases of MS without surgery, matched by a two-staged Propensity score match, including age at disease onset, sex, MS phenotype, body mass index, and preoperative severity of MS as measured by the Expanded Disability Status Scale.RESULTS: The time to 6-month confirmed disability progression during the first five years postbaseline was shorter among the surgical patients (hazard ratio (HR) = 2.31, 95% confidence interval (CI) = 1.09-4.90; p = 0.03). No differences were observed regarding postoperative annual relapse rate (p = 0.24) or time to first postoperative relapse (p = 0.52).CONCLUSION: Although metabolic surgery appears to be a safe and efficient treatment of obesity in patients with MS, the clinical course of the disease might be negatively affected. Long-term nutritional follow-up after surgery and supplementation maintenance are crucial, particularly among those with preoperative deficits.
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| 45. |
- Aronsson, Karin, et al.
(författare)
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Generationspositioner och förhandlingar vid middagsbordet
- 2010
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Ingår i: Barnets familjer ur barnkulturella perspektiv. - Stockholm : Centrum för barnkulturforskning. - 9197458864 - 9789197458863 ; , s. 23-38
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 46. |
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| 47. |
- Arvidsson, Per I., et al.
(författare)
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Open for collaboration : an academic platform for drug discovery and development at SciLifeLab
- 2016
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Ingår i: Drug Discovery Today. - : Elsevier BV. - 1359-6446 .- 1878-5832. ; 21:10, s. 1690-1698
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Forskningsöversikt (refereegranskat)abstract
- The Science for Life Laboratory Drug Discovery and Development (SciLifeLab DDD) platform reaches out to Swedish academia with an industry-standard infrastructure for academic drug discovery, supported by earmarked funds from the Swedish government. In this review, we describe the build-up and operation of the platform, and reflect on our first two years of operation, with the ambition to share learnings and best practice with academic drug discovery centers globally. We also discuss how the Swedish Teacher Exemption Law, an internationally unique aspect of the innovation system, has shaped the operation. Furthermore, we address how this investment in infrastructure and expertise can be utilized to facilitate international collaboration between academia and industry in the best interest of those ultimately benefiting the most from translational pharmaceutical research - the patients.
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| 48. |
- Babateen, Omar, et al.
(författare)
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Etomidate, propofol and diazepam potentiate GABA-evoked GABAA currents in a cell line derived from Human glioblastoma
- 2015
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Ingår i: European Journal of Pharmacology. - : Elsevier BV. - 0014-2999 .- 1879-0712. ; 748, s. 101-107
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Tidskriftsartikel (refereegranskat)abstract
- GABAA receptors are pentameric chloride ion channels that are opened by GABA. We have screened a cell line derived from human glioblastoma, U3047MG, for expression of GABAA receptor subunit isoforms and formation of functional ion channels. We identified GABAA receptors subunit α2, α3, α5, β1, β2, β3, δ, γ3, π, and θ mRNAs in the U3047MG cell line. Whole-cell GABA-activated currents were recorded and the half-maximal concentration (EC50) for the GABA-activated current was 36μM. The currents were activated by THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol) and enhanced by the benzodiazepine diazepam (1μM) and the general anesthetics etomidate and propofol (50μM). In line with the expressed GABAA receptors containing at least the α3β3θ subunits, the receptors were highly sensitive to etomidate (EC50=55nM). Immunocytochemistry identified expression of the α3 and β3 subunit proteins. Our results show that the GABAA receptors in the glial cell line are functional and are modulated by classical GABAA receptor drugs. We propose that the U3047MG cell line may be used as a model system to study GABAA receptors function and pharmacology in glial cells.
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| 49. |
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| 50. |
- Barash, Uri, et al.
(författare)
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Heparanase promotes glioma progression via enhancing CD24 expression
- 2019
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Ingår i: International Journal of Cancer. - : WILEY. - 0020-7136 .- 1097-0215. ; 145:6, s. 1596-1608
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Tidskriftsartikel (refereegranskat)abstract
- Heparanase is an endo-beta-d-glucuronidase that cleaves heparan sulfate (HS) side chains of heparan sulfate proteoglycans. Compelling evidence tie heparanase levels with all steps of tumor formation including tumor initiation, growth, metastasis and chemo-resistance, likely involving augmentation of signaling pathways and gene transcription. In order to reveal the molecular mechanism(s) underlying the protumorigenic properties of heparanase, we established an inducible (Tet-on) system in U87 human glioma cells and applied gene array methodology in order to identify genes associated with heparanase induction. We found that CD24, a mucin-like cell adhesion protein, is consistently upregulated by heparanase and by heparanase splice variant devoid of enzymatic activity, whereas heparanase gene silencing was associated with decreased CD24 expression. This finding was further substantiated by a similar pattern of heparanase and CD24 immunostaining in glioma patients (Pearson's correlation; R = 0.66, p = 0.00001). Noteworthy, overexpression of CD24 stimulated glioma cell migration, invasion, colony formation in soft agar and tumor growth in mice suggesting that CD24 functions promote tumor growth. Likewise, anti-CD24 neutralizing monoclonal antibody attenuated glioma tumor growth, and a similar inhibition was observed in mice treated with a neutralizing mAb directed against L1 cell adhesion molecule (L1CAM), a ligand for CD24. Importantly, significant shorter patient survival was found in heparanase-high/CD24-high tumors vs. heparanase-high/CD24-low tumors for both high-grade and low-grade glioma (p = 0.02). Our results thus uncover a novel heparanase-CD24-L1CAM axis that plays a significant role in glioma tumorigenesis.
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