| 1. |
- Segerman, Anna, et al.
(author)
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Clonal Variation in Drug and Radiation Response among Glioma-Initiating Cells Is Linked to Proneural-Mesenchymal Transition
- 2016
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In: Cell Reports. - : Elsevier BV. - 2211-1247. ; 17:11, s. 2994-3009
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Journal article (peer-reviewed)abstract
- Intratumoral heterogeneity is a hallmark of glioblastoma multiforme and thought to negatively affect treatment efficacy. Here, we establish libraries of glioma-initiating cell (GIC) clones from patient samples and find extensive molecular and phenotypic variability among clones, including a range of responses to radiation and drugs. This widespread variability was observed as a continuumof multitherapy resistance phenotypes linked to a proneural-mesenchymal shift in the transcriptome. Multitherapy resistance was associated with a semi-stable cell state that was characterized by an altered DNA methylation pattern at promoter regions of mesenchymal master regulators and enhancers. The gradient of cell states within the GIC compartment constitutes a distinct form of heterogeneity. Our findings may open an avenue toward the development of new therapeutic rationales designed to reverse resistant cell states.
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| 2. |
- Arnander, Claes, et al.
(author)
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Three-Dimensional Technology and Bone Morphogenetic Protein in Frontal Bone Reconstruction
- 2006
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In: Journal of Craniofacial Surgery. ; 17:2, s. 275-279
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Journal article (peer-reviewed)abstract
- Osteoinductive bone morphogenetic proteins (BMPs) may be used in humans to facilitate healing of bony defects. The effect of different BMPs is, as with many other growth factors, highly dependent on the delivery vehicle. Bovine type I collagen is currently used in the clinical setting as a carrier and has been approved in several countries for human use. Here, we report the reconstruction of a frontal bone defect using heparin together with bovine type I collagen, hyaluronic acid, and fibrin as vehicles for BMP-2. A bony structure was created on the back of the patient by treating the latissimus dorsi muscle with the growth factor. A polyamide mold was used as a template to achieve the desired shape. The bone structure was transplanted into the defect site via microsurgical techniques. Although the prefabricated bone was not large enough tocover the entire frontal defect, the reconstruction was completed by using an additional cranial implant.
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| 3. |
- Engstrand, Thomas, et al.
(author)
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A novel biodegradable delivery system for bone morphogenetic protein-2.
- 2008
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In: Plastic and reconstructive surgery. - 1529-4242. ; 121:6, s. 1920-8
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Journal article (peer-reviewed)abstract
- BACKGROUND: The efficacy of recombinant growth factors in vivo is highly dependent on the delivery vehicle. The authors investigated the osteoinductive effects of recombinant human bone morphogenetic proteins (BMP)-2 implanted together with a complex of heparin and chitosan. METHODS: Sixty rats were used. Three different carriers in gel formulation (type I collagen, heparin/type I collagen, and heparin/chitosan) were mixed with either 0, 10, or 50 microg of BMP-2, making the number of groups nine. The gels were injected into the quadriceps muscles of both legs in 45 rats (n = 10 per group). Freeze-dried formulations of the carriers were also tested with the same amounts of BMP-2 using 15 rats (n = 5 per group). Four weeks after implantation, the quality and amount of newly formed bone were assessed. RESULTS: Chitosan was shown to protect the heparinase-mediated degradation of heparin in vitro. The osteoinductive effects of BMP-2 in combination with heparin/chitosan were superior as compared with BMP-2 implanted together with type I collagen. Interestingly, the heparin/chitosan complex induced a small amount of bone also without BMP-2 added. The heparin/chitosan was completely absorbed after 4 weeks as determined by histologic evaluation, and a normal active bone formation was present. The freeze-dried formulations of the carriers demonstrated similar osteoinductive effects as the gels. CONCLUSIONS: An osteoinductive formula for clinical use is needed for general bone reconstruction. Heparin in complex with chitosan has the ability to stabilize or activate the growth factor in vivo and induce the generation of new bone in good yields.
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| 4. |
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| 5. |
- Molin, Lena, et al.
(author)
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Do personal experiences have an impact on teaching and didactic choices in geography?
- 2015
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In: European Journal of Geography. - : Association of European Geographers. - 1792-1341. ; 6:4, s. 6-20
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Journal article (peer-reviewed)abstract
- Factors influencing teachers’ selection of content in geography teaching is a fundamental didactic matter.1 The purpose of the present study was to investigate whether Swedish geography teachers’ informal and formal experiences have influenced their interest in geography and if so, in what way. The results disclosed that informal experiences like outings, holidays, and childhood memories have a significant impact. The results also revealed that childhood experiences might increase the comprehension of how nature and mankind are connected, and how various places differ. Selective traditions showed to be strong, i.e. geographic names and map reading were prioritized while at excursions, physical geography was particularly dominating. We argue that in the geography teacher education, didactics should include methods for field studies, giving emphasis also to the part dealing with human geography. Forthcoming teachers need to reflect on how to make didactic choices in order to renounce the selective traditions in the subject.
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| 6. |
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| 7. |
- Nyström, Anna-Maja, et al.
(author)
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Investigation of gene dosage imbalances in patients with Noonan syndrome using multiplex ligation-dependent probe amplification analysis
- 2010
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In: European Journal of Medical Genetics. - : Elsevier BV. - 1769-7212 .- 1878-0849. ; 53:3, s. 117-121
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Journal article (peer-reviewed)abstract
- The RAS-MAPK syndromes are a group of clinically and genetically related disorders caused by dysregulation of the RAS-MAPK pathway. A member of this group of disorders, Noonan syndrome (NS), is associated with several different genes within the RAS-MAPK pathway. To date, mutations in PTPN11, SOS1, KRAS, RAF1 and SHOC2 are known to cause NS and a small group of patients harbour mutations in BRAF, MEK1 or NRAS. The majority of the mutations are predicted to cause an up-regulation of the pathway; hence they are gain-of-function mutations. Despite recent advances in gene identification in NS, the genetic aetiology is still unknown in about of patients.To investigate the contribution of gene dosage imbalances of RAS-MAPK-related genes to the pathogenesis of NS, a multiplex ligation-dependent probe amplification (MLPA) assaywas developed. Two probe sets were designed for seven RAS-MAPK-syndrome-related candidate genes: PTPN11, SOS1, RAF1, KRAS, BRAF, MEK1 and MEK2. The probe sets were validated in 15 healthy control individuals and in glioma tumour cell lines. Subsequently, 44 NS patients negative for mutations in known NS-associated genes were screened using the two probe sets. The MLPA results for the patients revealed no gene dosage imbalances. In conclusion, the present results exclude copy number variation of PTPN11, SOS1, RAF1, KRAS, BRAF, MEK1 and MEK2 as a common pathogenic mechanism of NS. The validated and optimised RAS-MAPK probe sets presented here enable rapid high throughput screening of further patients with RAS-MAPK syndromes.
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| 8. |
- Olsson, Charlotta, et al.
(author)
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Determination of the frequencies of ten allelic variants of the Wilson disease gene (ATP7B), in pooled DNA samples
- 2000
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In: European Journal of Human Genetics. - 1018-4813 .- 1476-5438. ; 8:12, s. 933-938
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Journal article (peer-reviewed)abstract
- Wilson disease is an autosomal recessive disorder characterised by toxic accumulation of copper in liver, brain and other organs. The disorder is caused by mutations in the ATP7B gene, encoding a copper transporting P-type ATPase. Based on the number of known patients with this diagnosis in Sweden, the prevalence can be estimated to 1 in 250 000 to 300 000, whereas the prevalence of Wilson disease has been estimated to be 1 in 30 000 in other populations. We estimated the prevalence of Wilson disease by determining the Swedish population frequencies of two mutant alleles, making up approximately half the mutations in Swedish Wilson patients, in a large number of DNA samples. In addition we determined the allele frequencies of eight common single-nucleotide polymorphisms (SNPs) in the ATP7B gene. For the analyses we devised two strategies for analysing pooled DNA samples using the quantitative minisequencing method. The two procedures allowed sensitive identification of rare mutant alleles present as a mixture with an excess of the normal allele, as well as accurate estimation of the frequencies of the common SNPs in a large pooled DNA sample.
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| 9. |
- Persson, Ann L, et al.
(author)
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Validity of electrical stimulus magnitude matching in chronic pain
- 2009
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In: Journal of Rehabilitation Medicine. - 1650-1977 .- 1651-2081. ; 41:11, s. 898-903
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Journal article (peer-reviewed)abstract
- Objective: To examine the validity of the PainMatcher in chronic pain.Design: Comparison of parallel pain estimates from visual analogue scales with electrical stimulus magnitude matching.Patients: Thirty-one patients with chronic musculoskeletal pain.Methods: Twice a day ongoing pain was rated on a standard 100-mm visual analogue scale, and thereafter magnitude matching was performed using a PainMatcher. The sensory threshold to electrical stimulation was tested twice on separate occasions.Results: In 438 observations visual analogue scale ranged from 3 to 95 (median 41) mm, and PainMatcher magnitudes from 2.67 to 27.67 (median 6.67; mean 7.78) steps. There was little correlation between visual analogue scale and magnitude data (r = 0.29; p < 0.0001). The mean sensory threshold was 3.67 steps, indicating that the PainMatcher, on average, stimulated at 2.1 times the perception threshold at matching point.Conclusion: Electrical magnitude matching of chronic pain intensity elicited limited activation of nerve fibres at 2.0–2.2 times sensory threshold, indicating that the induced pain was evoked by coarse nociceptive Aδ fibres. While the visual analogue scale estimates covered the whole range of the instrument, the PainMatcher readings utilized only a small part of the instrument range and, importantly, had little or no relation to the visual analogue scale estimates. The validity of the PainMatcher procedure is doubtful.
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| 10. |
- Storå, Jan, et al.
(author)
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Osteologisk analys av skelettfynd från Verkstadsvägen : Arkeologi Motala
- 2020
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Reports (other academic/artistic)abstract
- Den osteologiska analysen av fyndmaterialet från Verkstadsvägen belyserpå ett konkret sätt både de mesolitiska aktiviteterna på platsen och utnyttjandetav slaktdjur under yngre tidsperioder. Vid Verkstadsvägen har fem områden med mesolitiska fynd identifierats,Hus 1–4 samt Hantverksområdet. Dessutom finns områden som ihögre grad påverkats av sentida aktiviteter och där benfynden till störstadel var yngre än från stenålder. Den osteologiska analysen har haftsom ett viktigt mål att försöka separera de mesolitiska skelettfynden frånyngre deponeringar. Den mest uppenbara mesolitiska fyndkategorin ärbenartefakter och bearbetade ben från benhantverk. Spridningen visaren tydlig koncentration till den centrala delen av undersökningsområdet– Hantverksområdet.Ett stort yngre benmaterial är tillvarataget inom kulturlager och kontextersom är påverkade av åkerbruk eller annan markanvändning. Detyngre materialet ger en bild av ett medvetet utnyttjande av kött från slaktdjur,där man valt ut de köttrikadelarna från djur som tycks ha föttsupp med inriktning på köttproduktion. De yngre deponeringarna ärdärmed till övervägande del resterefter matavfall. Det är inte otänkbartatt många ben är förknippademed den korvfabrik/salteri somtidigare legat på platsen.
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