| 1. |
- Englund, Anna-Lena, 1949-, et al.
(författare)
-
Värdegrunden reducerad till metod
- 2009
-
Ingår i: Pedagogiska magasinet. - Stockholm : Lärarförbundet. - 1401-3320. ; 13:4, s. 18-21
-
Tidskriftsartikel (populärvet., debatt m.m.)abstract
- Det behövs en etisk vändning i diskussionen om främjande och förebyggande program. Alltför stort intresse riktas mot frågan om evidens och effektivitet och alltför lite intresse riktas mot värdefrågorna. Vad innebäör det för lärarens professionalism om manualstyrda aktiviteter ersätter samtal och samspel?
|
|
| 2. |
|
|
| 3. |
- Graffmo, Karin Sixtensdotter, 1960-
(författare)
-
Of mice and men : SOD1 associated human amyotrophic lateral sclerosis and transgenic mouse models
- 2007
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Amyotrophic lateral sclerosis, ALS, is a progressive fatal neurodegenerative disorder affecting motor neurones in motor cortex, brain stem and spinal cord. This inevitably leads to paralysis, respiratory failure and death. In about 5% of patients with ALS there is an association with mutations in gene for the abundant intracellular scavenging enzyme superoxide dismutase1, SOD1. The noxious property of SOD1 is proposed to be due to gain of function. In familial cases the inheritance is most commonly dominant.This study focus on two disparate SOD1 mutations occurring in Scandinavia. The recessive D90A mutation which has properties similar to that of the normal wild-type human SOD1. The dominantly inherited G127insTGGG mutation, G127X, causes a C-terminal truncation of the last 21 amino acids and is a highly unstable protein.Transgenic mice were created expressing D90A and G127X mutated human SOD1. Results from studies of tissue from the central nervous system of patients carrying either of these mutations were compared with similar tissue collected from transgenic mice generated with the same mutations. Tissue from the mice were also compared to central nervous tissue from several other transgenic mouse strains expressing human wild type SOD1 as well as other ALS associated human SOD1 mutations.The transgenic mice expressing D90A respectively G127X mutated human SOD1 develop motor neurone disease. Microscopic studies of central nervous tissues from G127X transgenic mice reveals inclusions of aggregated misfolded SOD1 in motor neurones and adjacent supporting cells. These inclusions are composed of detergent resistant aggregates and preceded by accumulations of minute quantities of detergent-soluble aggregates. The inclusions mimic those found in G127X patients.In D90A transgenic mice the progression, as in the humans, was slower and the mice, as the patients, showed bladder disturbance. In the D90A patients, the SOD1 inclusions mimic those found in sporadic ALS patients.Aggregation of SOD1 in central nervous tissue appears to be related to severity of disease. Degenerative features as vacuolization and gliosis precedes phenotypic alterations. Changes are seen not only in motor areas but also in higher centres of the telencephalon.
|
|
| 4. |
- Kyhn, Maria Voss, et al.
(författare)
-
Delayed administration of glial cell line-derived neurotrophic factor (GDNF) protects retinal ganglion cells in a pig model of acute retinal ischemia
- 2009
-
Ingår i: Experimental Eye Research. - : Elsevier BV. - 0014-4835 .- 1096-0007. ; 89:6, s. 1012-1020
-
Tidskriftsartikel (refereegranskat)abstract
- This study investigates whether intravitreal administration of glial cell line-derived neurotrophic factor (GDNF) enhances survival of NeuN positive retinal cells in a porcine model of retinal ischemia. 16 pigs were subjected to an ischemic insult where intraocular pressure was maintained at 5 mmHg below mean arterial blood pressure for 2 h. The mean IOP during the ischemic insult was 79.5 mmHg (s.e.m. 2.1 mmHg, n = 15). Three days after the insult the pigs received an intravitreal injection of GDNF microspheres or blank microspheres. The pigs were evaluated by way of multifocal electroretinography (mfERG), quantification of NeuN positive cells and evaluation of the degree of retinal perivasculitis and inflammation 6 weeks after the insult. In the post-injection eyes (days 14, 28 and 42), the ratios of the iN1 and the iP2 amplitudes were 0.10 (95% CI: 0.05-0.15) and 0.09 (95% CI: 0.04-0.16) in eyes treated with blank microspheres, and 0.24 (95% CI: 0.18-0.32) and 0.23 (95% CI: 0.15-0.33) in eyes treated with GDNF microspheres. These differences were statistically significant (P < 0.05). The number of NeuN positive cells in the area of the visual streak area was significantly higher in eyes injected with GDNF microspheres compared to eyes injected with blank microspheres. In eyes injected with GDNF microspheres the ganglion cell count was 9.5/field (s.e.m.: 2.1, n = 8), in eyes injected with blank microspheres it was 3.5/field (s.e.m.: 1.2, n = 7). This difference was statistically significant (P < 0.05). There was also a significant difference (P < 0.01) in the degree of perivasculiitis between GDNF treated eyes (median perivasculitis score 1.5) and blank treated eyes (median perivasculitis score 3.0). In conclusion, injection of GDNF microspheres 3 days after an ischemic insult results in functional and morphological rescue of NeuN positive cells in a porcine model of acute ocular ischemia. (C) 2009 Elsevier Ltd. All rights reserved.
|
|
| 5. |
- Synnergren, Jane, 1967, et al.
(författare)
-
Cardiomyogenic gene expression profiling of differentiating human embryonic stem cells.
- 2008
-
Ingår i: Journal of biotechnology. - : Elsevier BV. - 0168-1656 .- 1873-4863. ; 134:1-2, s. 162-70
-
Tidskriftsartikel (refereegranskat)abstract
- Human embryonic stem cells (hESCs) can differentiate into a variety of specialized cell types. Thus, they provide a model system for embryonic development to investigate the molecular processes of cell differentiation and lineage commitment. The development of the cardiac lineage is easily detected in mixed cultures by the appearance of spontaneously contracting areas of cells. We performed gene expression profiling of undifferentiated and differentiating hESCs and monitored 468 genes expressed during cardiac development and/or in cardiac tissue. Their transcription during early differentiation of hESCs through embryoid bodies (EBs) was investigated and compared with spontaneously differentiating hESCs maintained on feeders in culture without passaging (high-density (HD) protocol). We observed a larger variation in the gene expression between cells from a single cell line that were differentiated using two different protocols than in cells from different cell lines that were cultured according to the same protocol. Notably, the EB protocol resulted in more reproducible transcription profiles than the HD protocol. The results presented here provide new information about gene regulation during early differentiation of hESCs with emphasis on the cardiomyogenic program. In addition, we also identified regulatory elements that could prove critical for the development of the cardiomyocyte lineage.
|
|
| 6. |
- Synnergren, Jane, 1967, et al.
(författare)
-
Differentiating human embryonic stem cells express a unique housekeeping gene signature.
- 2007
-
Ingår i: Stem cells (Dayton, Ohio). - : Oxford University Press (OUP). - 1066-5099 .- 1549-4918. ; 25:2, s. 473-80
-
Tidskriftsartikel (refereegranskat)abstract
- Housekeeping genes (HKGs) are involved in basic functions needed for the sustenance of the cell and are assumed to be constitutively expressed at a constant level. Based on these features, HKGs are frequently used for normalization of gene expression data. In the present study, we used the CodeLink Gene Expression Bioarray system to interrogate changes in gene expression occurring during differentiation of human ESCs (hESCs). Notably, in the three hESC lines used for the study, we observed that the RNA levels of 56 frequently used HKGs varied to a degree that rendered them inappropriate as reference genes. Therefore, we defined a novel set of HKGs specifically for hESCs. Here we present a comprehensive list of 292 genes that are stably expressed (coefficient of variation <20%) in differentiating hESCs. These genes were further grouped into high-, medium-, and low-expressed genes. The expression patterns of these novel HKGs show very little overlap with results obtained from somatic cells and tissues. We further explored the stability of this novel set of HKGs in independent, publicly available gene expression data from hESCs and observed substantial similarities with our results. Gene expression was confirmed by real-time quantitative polymerase chain reaction analysis. Taken together, these results suggest that differentiating hESCs have a unique HKG signature and underscore the necessity to validate the expression profiles of putative HKGs. In addition, this novel set of HKGs can preferentially be used as controls in gene expression analyses of differentiating hESCs.
|
|
| 7. |
- Synnergren, Jane, et al.
(författare)
-
Differentiating human embryonic stem cells express a unique housekeeping gene signature
- 2006
-
Ingår i: 4th ISSCR Annual Meeting.
-
Konferensbidrag (refereegranskat)abstract
- Human embryonic stem cells (hESCs) represent populations of pluripotent undifferentiated cells with unlimited replication capacity which can be coaxed to differentiate into a variety of specialized cells. As a result, there is great hope that hESCs will be extremely useful by providing platforms for various in vitro applications (e.g. in drug discovery) as well as for future use of hESCs and their differentiated progeny in cell replacement therapies. In order to realize the potential of hESCs, it is necessary to gain much deeper knowledge about the processes that govern differentiation of these cells.In recent years, significant progress towards understanding cellular differentiation has been fuelled, in part, by studying gene expression using microarrays. In this large scale studies, statistical methods are used to normalize the gene expression data and render comparisons between different samples. In lower throughput analyses, RNA levels in hESCs are also measured using RT-PCR requiring normalization of the gene expression data to adequately correct for inter-sample variation. In general, investigators have used the traditional housekeeping genes (HKGs) (e.g. GAPDH, b-tubulin, b-actin) in studies of hESCs. HKGs are involved in basic functions needed for the sustenance of the cell and are assumed to be constitutively expressed at a constant level. Based on these features, HKGs are frequently used for normalization of gene expression data. However, it is well known that the expression of several of these genes vary considerably in adult tissues and their suitability as HKGs in hESCs remains to be proven. In this regard, the RNA levels of HPRT and b-tubulin were shown to vary substantially in differentiating mouse ESCs.In the present study, we used the CodeLinkTM Gene Expression Bioarray system to interrogate changes in gene expression occurring during differentiation of hESCs. Notably, in the three hESC lines used for the study, we observed that the RNA levels of 56 frequently used HKGs varied to a degree that rendered them inappropriate as reference genes. Therefore, we defined a novel set of HKGs specifically for hESCs. Here we present a comprehensive list of 292 genes that are stably expressed (coefficient of variation<20%) in differentiating hESCs. These genes were further grouped into high, medium, and low expressed genes. The expression patterns of these novel HKGs show very little overlap with results obtained from somatic cells and tissues. We further explored the stability of this novel set of HKGs in independent, publicly available gene expression data from hESCs and observed substantial similarities in terms of stably expressed genes. Taken together, these results suggest that hESCs have a unique HKG signature and underscore the necessity to validate the expression profiles of putative HKGs. In addition, the novel set of identified HKGs can preferentially be used as controls in gene expression analyses of differentiating hESCs.
|
|
