| 1. |
- Skoog, Ingmar, 1954, et al.
(författare)
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Association between APOE Genotype and Change in Physical Function in a Population-Based Swedish Cohort of Older Individuals Followed Over Four Years
- 2016
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Ingår i: Frontiers in Aging Neuroscience. - : Frontiers Media SA. - 1663-4365. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- The association between decline in physical function and age-related conditions, such as reduced cognitive performance and vascular disease, may be explained by genetic influence on shared biological pathways of importance for aging. The apolipoprotein F (APOE) gene is well-known for its association with Alzheimer's disease, but has also been related to other disorders of importance for aging. The aim of this study was to investigate possible associations between APOE allele status and physical function in a population-based longitudinal study of older individuals. In 2005, at the age of 75, 622 individuals underwent neuropsychiatric and physical examinations, including tests of physical function, and APOE-genotyping. Follow-up examinations were performed at age 79. A significantly larger decline in grip strength (p = 0.015) between age 75 and 79 was found when comparing APOE epsilon 4 allele carriers with non carriers [10.3 (+/- 10.8) kg versus 7.8 (+/- 10.1) kg]. No association was seen with decline in gait speed, chair-stand, or balance. The association with grip strength remained after correction for cognitive and educational level, depression, cardiovascular disease, stroke, and BMI.
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| 2. |
- Anvret, Anna, et al.
(författare)
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DJ-1 Mutations are Rare in a Swedish Parkinson Cohort.
- 2011
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Ingår i: The open neurology journal. - 1874-205X. ; 5, s. 8-11
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Tidskriftsartikel (refereegranskat)abstract
- Mutations in the PARK7 gene, DJ-1, have been reported to cause early-onset and familial Parkinson's disease (PD). The function of DJ-1 and how it contributes to the development of the disease is not clear today, but several studies report that DJ-1 is responsive to oxidative stress and important for the maintenance of mitochondria. We have screened three coding regions of DJ-1 (exon 2, 5 and 7) in a Swedish Parkinson cohort. The Swedish PD material consisted of 67 patients with a self reported positive family history of PD and 77 patients with early-onset of disease (≤50 years old). We detected two patients with the previously reported synonymous mutation, Ala167Ala (c.501A>G, rs71653621), in exon 7. No Ala167Ala carriers were identified among 213 neurologically healthy Swedish controls. Mechanisms by which the synonymous Ala167Ala mutation can have consequences are unknown. It may affect the mRNA stability, secondary structure of mRNA, synthesis, turnover, protein folding and function. We could show a 1.3% decrease in DJ-1 mRNA folding energy in the A
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| 3. |
- Anvret, Anna, et al.
(författare)
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Possible involvement of a mitochondrial translation initiation factor 3 variant causing decreased mRNA levels in Parkinson's disease.
- 2010
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Ingår i: Parkinson's disease. - : Hindawi Limited. - 2042-0080. ; 2010
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Tidskriftsartikel (refereegranskat)abstract
- Genes important for mitochondrial function have been implicated in Parkinson's disease (PD). Mitochondrial translation initiation factor 3 (MTIF3) is a nuclear encoded protein required for the initiation of complex formation on mitochondrial ribosomes. Dysfunction of MTIF3 may impair mitochondrial function and dopamine neurons appear to be particularly vulnerable to oxidative stress, which may relate to their degeneration in PD. An association was recently reported between the synonymous rs7669(C>T) in MTIF3 and PD in a German case-control material. We investigated rs7669 in a Swedish Parkinson case-control material. The study revealed no significant association of the individual genotypes or alleles with PD. When comparing the combined TT/CT-genotypes versus the CC-genotype, we observed a significant association (P = .0473) with PD. We also demonstrated that the TT-genotype causes a significant decrease in MTIF3 mRNA expression compared to the CC-genotype (P = .0163). Our findings support the hypothesis that MTIF3 may be involved in the etiology of PD.
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| 4. |
- Bergman, Olle, 1978, et al.
(författare)
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Do polymorphisms in transcription factors LMX1A and LMX1B influence the risk for Parkinson's disease?
- 2009
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Ingår i: Journal of neural transmission (Vienna, Austria : 1996). - : Springer Science and Business Media LLC. - 1435-1463 .- 0300-9564. ; 116:3, s. 333-8
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Tidskriftsartikel (refereegranskat)abstract
- The key symptoms of Parkinson's disease (PD) are caused by degeneration of dopamine neurons originating in substantia nigra. Whereas, transcription factor LMX1A is crucial for the differentiation of mesencephalic dopamine neurons, LMX1B appears to be important for both the development and the survival of these cells. The aim of this study was to investigate if genetic variation in LMX1A and LMX1B differs between patients with PD (n = 357) and control subjects (n = 1428) by genotyping 33 single nucleotide polymorphisms (SNPs) in LMX1A and 11 SNPs in LMX1B. Three SNPs in LMX1A and one in LMX1B were associated with PD. After splitting for gender, six SNPs were associated with PD in women and four in men. The significances obtained did not survive correction for multiple testing, and our results should hence be interpreted with caution, but are partly in line with a previous report, and should thus be of sufficient interest to encourage further studies of these genes in PD.
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| 5. |
- Bergman, Olle, 1978, et al.
(författare)
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PITX3 polymorphism is associated with early onset Parkinson's disease.
- 2010
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Ingår i: Neurobiology of aging. - : Elsevier BV. - 1558-1497 .- 0197-4580. ; 31:1, s. 114-117
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Tidskriftsartikel (refereegranskat)abstract
- PITX3 is a transcription factor of importance for the differentiation and survival of midbrain dopaminergic neurons, the gene of which is disrupted in a putative mouse model for Parkinson's disease (PD). The A-allele of a HapMap tagging SNP (rs4919621) that was genotyped in a population of 361 PD patients, 69 of which had early onset, and in 333 controls, was significantly more common in PD patients with an early age of onset when compared either to controls (p=0.002) or to PD patients with late onset (p=0.001). In contrast, a previous finding suggesting a SNP (rs3758549) in the putative promoter region of the PITX3 gene to be associated with PD could not be replicated.
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| 6. |
- Håkansson, Anna, 1978, et al.
(författare)
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Cyclooxygenase-2 polymorphisms in Parkinson's disease.
- 2007
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Ingår i: American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics. - : Wiley. - 1552-4841. ; 144:3, s. 367-9
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Tidskriftsartikel (refereegranskat)abstract
- Accumulating evidence indicate that cyclooxygenase-2 (COX-2) is of pathophysiological importance for the neurodegeneration in Parkinson's disease (PD). For example, in a large epidemiological study, use of NSAIDs was associated with a lower risk of PD. Genetic variants of the COX-2 gene might therefore influence the risk of developing the disease. The genotype distribution of four common single nucleotide polymorphisms (SNPs) in the COX-2 gene (rs689466:A496G, rs20417:G926C, rs5277:G3050C, rs5275:C8473T) was analyzed in PD patients and control subjects in a Swedish population. No differences could be seen between the PD-patient and controls regarding the A496G, G926C, and G3050C SNPs, but the allele frequency of the C8473T SNP was found to differ when male patients were compared to controls (P = 0.007). In females no difference could be seen between PD-patients and controls. In conclusion, the results suggest a possible influence of the COX-2 C8473T SNP in PD, although it only seems to be of importance in men.
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| 7. |
- von Otter, Malin, 1978, et al.
(författare)
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Association of Nrf2-encoding NFE2L2 haplotypes with Parkinson's disease.
- 2010
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Ingår i: BMC medical genetics. - : Springer Science and Business Media LLC. - 1471-2350. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Oxidative stress is heavily implicated in the pathogenic process of Parkinson's disease. Varying capacity to detoxify radical oxygen species through induction of phase II antioxidant enzymes in substantia nigra may influence disease risk. Here, we hypothesize that variation in NFE2L2 and KEAP1, the genes encoding the two major regulators of the phase II response, may affect the risk of Parkinson's disease. METHODS: The study included a Swedish discovery case-control material (165 cases and 190 controls) and a Polish replication case-control material (192 cases and 192 controls). Eight tag single nucleotide polymorphisms representing the variation in NFE2L2 and three representing the variation in KEAP1 were chosen using HapMap data and were genotyped using TaqMan Allelic Discrimination. RESULTS: We identified a protective NFE2L2 haplotype in both of our European case-control materials. Each haplotype allele was associated with five years later age at onset of the disease (p = 0.001) in the Swedish material, and decreased risk of PD (p = 2 x 10(-6)), with an odds ratio of 0.4 (95% CI 0.3-0.6) for heterozygous and 0.2 (95% CI 0.1-0.4) for homozygous carriers, in the Polish material. The identified haplotype includes a functional promoter haplotype previously associated with high transcriptional activity. Genetic variation in KEAP1 did not show any associations. CONCLUSION: These data suggest that variation in NFE2L2 modifies the Parkinson's disease process and provide another link between oxidative stress and neurodegeneration.
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| 8. |
- von Otter, Malin, 1978, et al.
(författare)
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Kinesin Light Chain 1 Gene Haplotypes in Three Conformational Diseases
- 2010
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Ingår i: NeuroMolecular Medicine. - : Springer Science and Business Media LLC. - 1535-1084 .- 1559-1174. ; 12:3, s. 229-236
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Tidskriftsartikel (refereegranskat)abstract
- A functional intracellular transport system is essential to maintain cell shape and function especially in elongated cells, e.g. neurons and lens fibre cells. Impaired intracellular transport has been suggested as a common pathological mechanism for age-related diseases characterised by protein aggregation. Here, we hypothesise that common genetic variation in the transport protein kinesin may influence the risk of Parkinson's disease (PD), Alzheimer's disease (AD) and age-related cataract. This case-control study involves a PD material (165 cases and 190 controls), an AD material (653 cases and 845 controls) and a cataract material (495 cases and 183 controls). Genetic variation in the kinesin light chain 1-encoding gene (KLC1) was tagged by six tag single nucleotide polymorphisms (SNPs). Single SNPs and haplotypes were analysed for associations with disease risk, age parameters, mini-mental state examination scores and cerebrospinal fluid biomarkers for AD using logistic or linear regression. Genetic variation in KLC1 did not influence risk of PD. Weak associations with risk of AD were seen for rs8007903 and rs3212079 (P (c) = 0.04 and P (c) = 0.02, respectively). Two SNPs (rs8007903 and rs8702) influenced risk of cataract (P (c) = 0.0007 and P (c) = 0.04, respectively). However, the allele of rs8007903 that caused increased risk of AD caused reduced risk of cataract, speaking against a common functional effect of this particular SNP in the two diseases. Haplotype analyses did not add significantly to the associations found in the single SNP analyses. Altogether, these results do not convincingly support KLC1 as a major susceptibility gene in any of the studied diseases, although there is a small effect of KLC1 in relation to cataract.
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| 9. |
- Westerlund, Marie, et al.
(författare)
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Association of a polymorphism in the ABCB1 gene with Parkinson's disease.
- 2009
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Ingår i: Parkinsonism & related disorders. - : Elsevier BV. - 1353-8020 .- 1873-5126. ; 15:6, s. 422-424
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Tidskriftsartikel (refereegranskat)abstract
- The ATP-binding cassette, sub-family B, member 1 (ABCB1) gene encoding the protein P-glycoprotein (P-gp) has been implicated in the pathophysiology of Parkinson's disease (PD) due to its role in regulating transport of endogenous molecules and exogenous toxins. In the present study, we analyzed the ABCB1 single nucleotide polymorphisms (SNPs) 1236C/T (exon 12), 2677G/T/A (exon 21) and 3435C/T (exon 26) in 288 Swedish PD patients and 313 control subjects and found a significant association of SNP 1236C/T with disease (p=0.0159; chi(2)=8.28), whereas the distributions of wild-type and mutated alleles were similar for 2677G/T/A and 3435C/T in patients and controls. Haplotype analysis revealed significant association of the 1236C-2677G haplotype with PD (p=0.026; chi(2)=4.955) and a trend towards association with disease of the 1236C-2677G-3435C haplotype (p=0.072; chi(2)=3.229). Altered ABCB1 and/or P-pg expression was recently shown in PD patients, and impaired drug efflux across barriers such as the gastrointestinal and nasal mucosal linings or the blood-brain barrier, might result in accumulation of drugs and/or endogenous molecules in toxic amounts, possibly contributing to disease. ABCB1 polymorphisms thus constitute an example of how genetic predisposition and environmental influences may combine to increase risk of PD.
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| 10. |
- Westerlund, Marie, et al.
(författare)
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Cerebellar alpha-synuclein levels are decreased in Parkinson's disease and do not correlate with SNCA polymorphisms associated with disease in a Swedish material.
- 2008
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Ingår i: The FASEB journal : official publication of the Federation of American Societies for Experimental Biology. - : Wiley. - 1530-6860. ; 22:10, s. 3509-14
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Tidskriftsartikel (refereegranskat)abstract
- Alterations of brain and plasma alpha-synuclein levels and SNCA gene variability have been implicated in the pathogenesis of Parkinson's disease (PD). We therefore measured alpha-synuclein protein levels in postmortem PD and control cerebellum tissue using Western blot and investigated whether the levels correlated to SNCA genotype. We found markedly decreased alpha-synuclein levels in PD patients (n=16) compared to gender- and age-matched controls (n=14; P=0.004) normalized to alpha-tubulin. We also performed an association study of the noncoding polymorphisms rs2737029 (A/G) and rs356204 (A/G) (intron 4), and of rs356219 (T/C) (3'-region) of SNCA in a Swedish PD case-control material. Using a two-sided chi(2) test, we found significant association of rs2737029 (P=0.003; chi(2)=9.07) and rs356204 (P=0.048; chi(2)=3.91) with disease, strengthening the involvement of SNCA polymorphisms in sporadic PD. Stratification of the human postmortem brain material by genotype of the three investigated polymorphisms, did not indicate any influence of genotype on alpha-synuclein protein levels when comparing PD with controls. Taken together, our findings demonstrate that the investigated Parkinson patients have markedly reduced levels of alpha-synuclein in cerebellum, and that this reduction is general, rather then correlated to the investigated polymorphisms, although two of the polymorphisms also associated with disease in a Swedish material.
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| 11. |
- Ahmadi, Ahmad, et al.
(författare)
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Association of a protective paraoxonase 1 (PON1) polymorphism in Parkinson's disease
- 2012
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Ingår i: Neuroscience Letters. - : Elsevier BV. - 0304-3940 .- 1872-7972. ; 522:1, s. 30-35
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Tidskriftsartikel (refereegranskat)abstract
- Pesticide exposure has been suggested to increase the risk to develop Parkinson's disease (PD). The arylesterase paraoxonase 1 (PON1) is mainly expressed in the liver and hydrolyzes organophosphates such as pesticides. The polymorphism Leu54Met (rs854560) in PON1, impairing enzyme activity and leading to decreased PON1 expression levels, has been reported to be associated with Parkinson's disease (PD). PON1 is part of a cluster on chromosome 7q21.3 together with PON2 and PON3. We investigated the occurrence of four additional polymorphisms in PON1 and two in PON2 in a Swedish PD case-control material. We found a significant association (p = 0.007) with a PON1 promoter polymorphism, rs854571. The minor allele was more common among controls than PD cases which suggest a protective effect. This is strengthened by the fact that rs854571 is in strong linkage disequilibrium with another PON1 promoter polymorphism, rs854572, reported to increase PON1 gene expression. Our findings support the hypothesis that PON1 is involved in the etiology of PD and that higher PON1 levels are reducing the risk for PD. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
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| 12. |
- Belin, Andrea Carmine, et al.
(författare)
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Association study of two genetic variants in mitochondrial transcription factor A (TFAM) in Alzheimer's and Parkinson's disease.
- 2007
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Ingår i: Neuroscience letters. - : Elsevier BV. - 0304-3940. ; 420:3, s. 257-62
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Tidskriftsartikel (refereegranskat)abstract
- Mitochondrial (mt) dysfunction has been implicated in Alzheimer's (AD) and Parkinson's disease (PD). Mitochondrial transcription factor A (TFAM) is needed for mtDNA maintenance, regulating mtDNA copy number and is absolutely required for transcriptional initiation at mtDNA promoters. Two genetic variants in TFAM have been reported to be associated with AD in a Caucasian case-control material collected from Germany, Switzerland and Italy. One of these variants was reported to show a tendency for association with AD in a pooled Scottish and Swedish case-control material and the other variant was reported to be associated with AD in a recent meta-analysis. We investigated these two genetic variants, rs1937 and rs2306604, in an AD and a PD case-control material, both from Sweden and found significant genotypic as well as allelic association to marker rs2306604 in the AD case-control material (P=0.05 and P=0.03, respectively), where the A-allele appears to increase risk for developing AD. No association was observed for marker rs1937. We did not find any association in the PD case-control material for either of the two markers. The distribution of the two-locus haplotype frequencies (based on rs1937 and rs2306604) did not differ significantly between affected individuals and controls in the two sample sets. However, the global P-value for haplotypic association testing indicated borderline association in the AD sample set. Our data suggests that the rs2306604 A-allele could be a moderate risk factor for AD, which is supported by the recent meta-analysis.
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| 13. |
- Berbyuk, Nataliya, 1978, et al.
(författare)
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Multimodal human-horse interaction in therapy and leisure riding
- 2015
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Ingår i: Jokinen, K. & Vels, M. (eds) Proceedings of the 2nd European and the 5th Nordic Symposium on Multimodal Communication, August 6-8, 2014. Tartu, Estonia. 110:009. http://www.ep.liu.se/ecp_home/index.en.aspx?issue=110 (5/27/2015) Linköping: LiU Electronic Press.. - 1650-3686. - 9789175190747
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Konferensbidrag (refereegranskat)
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| 14. |
- Carmine Belin, Andrea, et al.
(författare)
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Leucine-rich repeat kinase 2 (LRRK2) mutations in a Swedish Parkinson cohort and a healthy nonagenarian.
- 2006
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Ingår i: Movement disorders : official journal of the Movement Disorder Society. - : Wiley. - 0885-3185. ; 21:10, s. 1731-4
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Tidskriftsartikel (refereegranskat)abstract
- Specific variants of Leucine-rich repeat kinase 2 (LRRK2) have been shown to associate with Parkinson's disease (PD). Several mutations have been found in PD populations from different parts of the world. We investigated the occurrence of three mutations (R1441G/C/H, G2019S, and I2020T) in our Swedish case-control material and identified four carriers of the G2019S mutation in 284 PD cases and 1 95-year-old carrier in 305 controls. The other two variants were absent in our material. We conclude that the LRRK2 G2019S mutation constitutes a significant factor for PD in the Swedish population and that it is not completely penetrant.
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| 15. |
- Garre, Elena, 1978, et al.
(författare)
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Breast Cancer Patient-Derived Scaffolds Can Expose Unique Individual Cancer Progressing Properties of the Cancer Microenvironment Associated with Clinical Characteristics
- 2022
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 14:9
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Tidskriftsartikel (refereegranskat)abstract
- Simple Summary Despite huge progress in cancer diagnostics and medicine we still lack optimal cancer treatments for patients with aggressive diseases. This problem can be influenced by the biological heterogeneity of cancer cells as well as poorly understood cancer promoting effects of the cancer microenvironment being an important part of the cancer niche. In this study we have specifically monitored the activity of the cancer microenvironment in breast cancer patients using cell-free scaffolds repopulated with reporter cancer cells sensing the activity of the patient environment. The data show that scaffold induced changes in epithelial-mesenchymal transition and pluripotency markers were linked to clinical and prognostic properties of the original cancer and the information was even more precise when matching estrogen receptor status in our system. The findings highlight that patient-derived scaffolds uncover important information about varying malignant promoting properties in the cancer niche and can be used as a complementary diagnostic tool. Breast cancer is a heterogeneous disease in terms of cellular and structural composition, and besides acquired aggressive properties in the cancer cell population, the surrounding tumor microenvironment can affect disease progression and clinical behaviours. To specifically decode the clinical relevance of the cancer promoting effects of individual tumor microenvironments, we performed a comprehensive test of 110 breast cancer samples using a recently established in vivo-like 3D cell culture platform based on patient-derived scaffolds (PDSs). Cell-free PDSs were recellularized with three breast cancer cell lines and adaptation to the different patient-based microenvironments was monitored by quantitative PCR. Substantial variability in gene expression between individual PDS cultures from different patients was observed, as well as between different cell lines. Interestingly, specific gene expression changes in the PDS cultures were significantly linked to prognostic features and clinical information from the original cancer. This link was even more pronounced when ER alpha-status of cell lines and PDSs matched. The results support that PDSs cultures, including a cancer cell line of relevant origin, can monitor the activity of the tumor microenvironment and reveal unique information about the malignancy-inducing properties of the individual cancer niche and serve as a future complementary diagnostic tool for breast cancer.
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| 16. |
- Gustafsson, Anna W, et al.
(författare)
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Ord på prov : En studie av ordförståelse i högskoleprovet
- 2017
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Bok (övrigt vetenskapligt/konstnärligt)abstract
- During the 1970s, vocabulary knowledge was a central topic within the field of Swedish sociolinguistics, often discussed from a democratic point of view focusing on inclusion and accessibility in the society. This study links up to this tradition by reporting a survey of how the vocabulary knowledge has changed over time in Sweden, building on data from theSwedish Scholastic Aptitude Test (SweSAT). Ever since 1977, SweSAT has functioned as an instrument of selection to higher education. SweSAT consists of different quantitative and verbal subtests, and one of these subtest, the vocabulary test, is intended to assess understanding of words and concepts. The SweSAT vocabulary test is a multiple-choice test where no context is given. The study has been limited to comprise the period from the spring 2000 to the spring 2011. During this period, the vocabulary test consisted of 40 tasks at each occasion and was carried out by about40.000 participants each time. Based on data from the SweSAT vocabulary test, two substudies have been carried out. The first of these substudies focuses on differences in average test results over time. Since SweSAT is designed to rank the test takers as fairly as possible with regard to their expected study success,different tests are however not directly comparable. One solution to this problem is to restrict the comparison over time to different groups (i.e.based on age, educational background, and gender) in order to establish how the vocabulary knowledge has changed over time. The first substudy reports such an investigation of comparisons between groups, building on answers from 915, 491 participants. Over time, the average test score at the vocabulary test has decreased with about 2 points. During the same period we see a widening gap between different age groups. This widening gap can also be noticed when comparing test takers with or without university education. Other variables are of limited importance to explain the variation in test scores. A comparison of the average test score over time can, of course, not give any information of how the understanding of individual words has changed over time. However, every word that is given in a regular vocabulary test has previously been tried out on a smaller group of participants in connection with a regular SweSAT test (the test takers learn afterwards which part of the test that consisted of pretest tasks and which parts belonged to the regular test). By comparing the results for individual words from the pretests with the corresponding result from the regular test, changes in the understanding of individual words can however be tracked. The second substudy reports such an investigation of comparisons between pretests and regular vocabulary tests, building on results for a selection of151 words. When comparing the results from the pretests with the regular vocabulary tests, 110 of the 151 words included have changed significantly over time. For 75 of the words included (49%), the results have decreased between the pretests and the regular tests, whereas 36 (24%) of the words display a significant increase. As was the case in the first substudy, there are clear differences between age-groups, whereas the difference between females and males is almost non-existent. When looking for possible explanations of the results demonstrated, some tendencies to a connection between the improvement and frequency have been found, whereas no such relationship could be supported for the words that show a decreased result over time. However, there is a clear connection between vocabulary knowledge and word origin in the sense that words used also in English shows a better result than domestic words.
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| 17. |
- Gustafsson, Anna W, et al.
(författare)
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Språkklyftan : 30 år senare
- 2011
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Ingår i: Svenskans beskrivning. - Lund : Lund University Press. - 1102-3619 .- 0282-7182. - 9789188466792 ; , s. 123-132
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Bokkapitel (refereegranskat)
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| 18. |
- Gustafsson, Anna W., et al.
(författare)
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Unga förstår allt färre ord
- 2017
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Ingår i: Språktidningen. - 1654-5028. ; :8, s. 24-29
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- De ungas ordförråd har krympt de senaste årtiondena, medan de äldres har vuxit. Högskoleprovet avslöjar en verklighet som kan hota demokratin.
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| 19. |
- Hansson, Mattias, et al.
(författare)
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Artifactual insulin release from differentiated embryonic stem cells.
- 2004
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Ingår i: Diabetes. - 0012-1797. ; 53:10, s. 2603-9
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Tidskriftsartikel (refereegranskat)abstract
- Several recent reports claim the generation of insulin-producing cells from embryonic stem cells via the differentiation of progenitors that express nestin. Here, we investigate further the properties of these insulin-containing cells. We find that although differentiated cells contain immunoreactive insulin, they do not contain proinsulin-derived C-peptide. Furthermore, we find variable insulin release from these cells upon glucose addition, but C-peptide release is never detected. In addition, many of the insulin-immunoreactive cells are undergoing apoptosis or necrosis. We further show that cells cultured in the presence of a phosphoinositide 3-kinase inhibitor, which previously was reported to facilitate the differentiation of insulin(+) cells, are not C-peptide immunoreactive but take up fluorescein isothiocyanate-labeled insulin from the culture medium. Together, these data suggest that nestin(+) progenitor cells give rise to a population of cells that contain insulin, not as a result of biosynthesis but from the uptake of exogenous insulin. We conclude that C-peptide biosynthesis and secretion should be demonstrated to claim insulin production from embryonic stem cell progeny.
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| 20. |
- Henningsson, Susanne, 1977, et al.
(författare)
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Interleukin-6 gene polymorphism -174G/C influences plasma lipid levels in women.
- 2006
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Ingår i: Obesity (Silver Spring, Md.). - 1930-7381. ; 14:11, s. 1868-73
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Tidskriftsartikel (refereegranskat)abstract
- Elevated levels of the pro-inflammatory cytokine interleukin-6 (IL-6) have been associated with cardiovascular risk factors. The objective of this study was to investigate potential associations between the promoter polymorphism IL-6 -174G/C and the following indices of metabolism: BMI, waist-to-hip ratio, and plasma levels of IL-6, cholesterol, low-density lipoprotein, triglycerides, high-density lipoprotein, leptin, and C-reactive protein in 252 42-year-old women and 245 51-year-old men. Subgroups were also studied 5 years later. The CC genotype of the IL-6 polymorphism was associated with lower levels of cholesterol and low-density lipoprotein (p < 0.001) in women. This finding was replicated in the follow-up, when a significant association between the CC genotype and low triglycerides was also observed. The association between the C allele and lipid pattern found in women was not found in men, where on the contrary, C carriers tended to display elevated triglycerides. IL-6 genotype was not associated with IL-6 plasma levels in either sample. The results suggest different effects of the IL-6 polymorphism on metabolic indices in women and men. None of the associations between IL-6 genotype and lipid pattern seemed to result from an effect of the polymorphism on IL-6 plasma levels.
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| 21. |
- Håkansson, Anna, 1978, et al.
(författare)
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Interaction of polymorphisms in the genes encoding interleukin-6 and estrogen receptor beta on the susceptibility to Parkinson's disease.
- 2005
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Ingår i: American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics. - : Wiley. - 1552-4841 .- 1552-485X. ; 133:1, s. 88-92
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Tidskriftsartikel (refereegranskat)abstract
- The multifunctional cytokine interleukin-6 (IL-6) is involved in inflammatory processes in the central nervous system and increased levels of IL-6 have been found in patients with Parkinson's disease (PD). It is known that estrogen inhibits the production of IL-6, via action on estrogen receptors, thereby pointing to an important influence of estrogen on IL-6. In a previous study, we reported an association between a G/A single nucleotide polymorphism (SNP) at position 1730 in the gene coding for estrogen receptor beta (ERbeta) and age of onset of PD. To investigate the influence of a G/C SNP at position 174 in the promoter of the IL-6 gene, and the possible interaction of this SNP and the ERbeta G-1730A SNP on the risk for PD, the G-174C SNP was genotyped, by pyrosequencing, in 258 patients with PD and 308 controls. A significantly elevated frequency of the GG genotype of the IL-6 SNP was found in the patient group and this was most obvious among patients with an early age of onset (
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| 22. |
- Håkansson, Anna, 1978, et al.
(författare)
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Investigation of genes coding for inflammatory components in Parkinson's disease.
- 2005
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Ingår i: Movement disorders : official journal of the Movement Disorder Society. - : Wiley. - 0885-3185 .- 1531-8257. ; 20:5, s. 569-73
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Tidskriftsartikel (refereegranskat)abstract
- Several findings obtained recently indicate that inflammation may contribute to the pathogenesis in Parkinson's disease (PD). Genetic variants of genes coding for components involved in immune reactions in the brain might therefore influence the risk of developing PD or the age of disease onset. Five single nucleotide polymorphisms (SNPs) in the genes coding for interferon-gamma (IFN-gamma; T874A in intron 1), interferon-gamma receptor 2 (IFN-gamma R2; Gln64Arg), interleukin-10 (IL-10; G1082A in the promoter region), platelet-activating factor acetylhydrolase (PAF-AH; Val379Ala), and intercellular adhesion molecule 1 (ICAM-1; Lys469Glu) were genotyped, using pyrosequencing, in 265 patients with PD and 308 controls. None of the investigated SNPs was found to be associated with PD; however, the G1082A polymorphism in the IL-10 gene promoter was found to be related to the age of disease onset. Linear regression showed a significantly earlier onset with more A-alleles (P = 0.0095; after Bonferroni correction, P = 0.048), resulting in a 5-year delayed age of onset of the disease for individuals having two G-alleles compared with individuals having two A-alleles. The results indicate that the IL-10 G1082A SNP could possibly be related to the age of onset of PD.
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| 23. |
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| 24. |
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| 25. |
- Håkansson, Charlotta, 1971-
(författare)
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Greenhouse Gas Fluxes and Carbon Sequestration in Young Norway Spruce Stands : The Effects of Fertilization
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The enormous challenge of climate change is discussed and debated today because of its major impact on life on Earth. The forests have an important role to play as the plants absorb carbon dioxide (CO2) from the atmosphere through their photosynthesis and the growing tree retain carbon (C). Hence, the larger the growth the greater the carbon storage and climate benefit. The demand for wood and wood products is increasing as well as the ongoing debate about forest management. Therefore, alternative management methods to increase wood production is of interest and the effects these methods could have on climate change mitigation. In this context this Thesis deals with the effect of fertilization on carbon balance and growth in young forest as well as flows of the greenhouse gases, CO2, methane (CH4), and nitrous oxide (N2O) from forest land. In addition, it deals also with the reliability and comparability of different measurement methods which are compared with respect to the carbon balance.The studies have been carried out in a young mixed stand of Norway spruce (Picea abies (L.) Karst) and birch (Betula pendula and B.pubescens) on a storm-felled (Gudrun 2005) area in southern Sweden, Kronoberg county. Part of the area was fertilized with 150 kg N ha-1 everysecond year from 2014 and forward, while the other part was kept unfertilized. In the unfertilized part a dose experiment was set up where 0,150, 300, and 450 kg N ha-1 were added to investigate the impact of the different fertilizer levels on forest floor greenhouse gas fluxes. Chamber measurements of forest floor fluxes, eddy-flux measurements of stand net-fluxes and tree measurements of height, diameter and birch leaf biomass were conducted in different, occasionally overlapping, periods in the years 2013-2021.The results show that even if the flows of CO2 from the forest floor increase initially after a first standard fertilization, the effect decreases quickly. The net fluxes show that the stands become carbon sinks already eight years after the storm with a net uptake of about 18 ton CO2 ha-1 yr-1 of. The forest floor fluxes of CH4 and N2O also show a short-term effect of fertilization, however the levels are very low compared to CO2. The fertilization induced increase of total tree biomass growth increased with time. The results show that 12 and 15 years after regeneration, the fertilization compared to the control has increased the tree growth by 3.4 and 6.3 m3 ha-1 yr-1 and carbon storage by 4.7 and 8.7 ton C ha-1 yr-1 respectively.Comparison of measurement results of the Eddy-flux technique's netflows and chamber measurements of soil respiration together with tree growth shows the importance of calibrating the measurement methods when the results are later to be used in modeling future climate scenarios.
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| 26. |
- Håkansson, David, 1978-, et al.
(författare)
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Digital kultur ger unga ett annat språk
- 2017
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Ingår i: Svenska Dagbladet. - Stockholm. ; , s. 21-, s. 21-21
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Tidskriftsartikel (populärvet., debatt m.m.)
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| 27. |
- Håkansson, David, 1978-, et al.
(författare)
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Hur står det till med hierarkin?
- 2010
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Ingår i: Svensson och svenskan. - Lund : [Språk- och litteraturcentrum]. - 9789163356841 ; , s. 124-138
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 28. |
- Håkansson, David, 1978-, et al.
(författare)
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Språkvetenskapen i ett sammanhang
- 2017. - 1
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Ingår i: Varför språkvetenskap?. - Lund. - 9789144108902 ; , s. 13-17
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 29. |
- Johansson, Annica, 1969, et al.
(författare)
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TAU haplotype and the Saitohin Q7R gene polymorphism do not influence CSF Tau in Alzheimer's disease and are not associated with frontotemporal dementia or Parkinson's disease.
- 2005
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Ingår i: Neuro-degenerative diseases. - : S. Karger AG. - 1660-2854 .- 1660-2862. ; 2:1, s. 28-35
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Recent studies have described Saitohin(STH), a gene located in the human TAU gene. The corresponding protein shows a similar tissue expression to tau, which is involved in many neurodegenerative disorders including Alzheimer's disease (AD), frontotemporal dementia (FTD) and Parkinson's disease (PD). A single nucleotide polymorphism in the STH gene has been suggested to be involved in sporadic AD and is in complete linkage disequilibrium with the TAU haplotype H1. OBJECTIVE: A case-control study was performed to further explore the possible involvement of the STH Q7R polymorphism and the extended TAU haplotype in AD, FTD or PD. METHODS: Patients with AD (n = 398), FTD (n = 96) and PD (n = 105), and controls (n = 186) were genotyped for the STH polymorphism and/or the TAU haplotype. Genotype data were related to levels of total-tau, phospho-tau and Abeta(1-42) in cerebral spinal fluid (CSF) in more than 300 AD patients and to an amount of senile plaques and neurofibrillary tangles in the frontal cortex and hippocampus in patients with autopsy-confirmed AD. RESULTS: The STH Q7R polymorphism and the TAU haplotype were in complete linkage disequilibrium in all patients (AD and FTD) and controls investigated for both genes. There were no significant differences in genotype or allele distributions in AD, FTD or PD cases compared to controls. Neither TAU haplotype nor STH influenced CSF levels of total-tau, phospho-tau and Abeta(1-42) significantly. In AD patients with neuropathological scores of plaque and tangles, no associations with TAU haplotype and STH were found. CONCLUSION: We found no evidence that could support a major pathogenic role of STH and TAU haplotype in AD, FTD or PD.
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| 30. |
- Leiva, Maria Carmen, et al.
(författare)
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Breast cancer patient-derived scaffolds as a tool to monitor chemotherapy responses in human tumor microenvironments
- 2021
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Ingår i: Journal of Cellular Physiology. - : Wiley. - 0021-9541 .- 1097-4652. ; 236:6, s. 4709-4724
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Tidskriftsartikel (refereegranskat)abstract
- Breast cancer is a heterogeneous disease where the tumor microenvironment, including extracellular components, plays a crucial role in tumor progression, potentially modulating treatment response. Different approaches have been used to develop three-dimensional models able to recapitulate the complexity of the extracellular matrix. Here, we use cell-free patient-derived scaffolds (PDSs) generated from breast cancer samples that were recellularized with cancer cell lines as an in vivo-like culture system for drug testing. We show that PDS cultured MCF7 cancer cells increased their resistance against the front-line chemotherapy drugs 5-fluorouracil, doxorubicin and paclitaxel in comparison to traditional two-dimensional cell cultures. The gene expression of the environmentally adapted cancer cells was modulated in different ways depending on the drug and the concentration used. High doses of doxorubicin reduced cancer stem cell features, whereas 5-fluorouracil increased stemness and decreased the proliferative phenotype. By using PDSs repopulated with other breast cancer cell lines, T-47D and MDA-MB-231, we observed both general and cell line specific drug responses. In summary, PDSs can be used to examine the extracellular matrix influence on cancer drug responses and for testing novel compounds in in vivo-like microenvironments.
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| 31. |
- Maier, Hannes, et al.
(författare)
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Consensus Statement on Bone Conduction Devices and Active Middle Ear Implants in Conductive and Mixed Hearing Loss
- 2022
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Ingår i: Otology and Neurotology. - : Lippincott, Williams & Wilkins. - 1531-7129 .- 1537-4505. ; 43:5, s. 513-529
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Tidskriftsartikel (refereegranskat)abstract
- Nowadays, several options are available to treat patients with conductive or mixed hearing loss. Whenever surgical intervention is not possible or contra-indicated, and amplification by a conventional hearing device (e.g., behind-the-ear device) is not feasible, then implantable hearing devices are an indispensable next option. Implantable bone-conduction devices and middle-ear implants have advantages but also limitations concerning complexity/invasiveness of the surgery, medical complications, and effectiveness. To counsel the patient, the clinician should have a good overview of the options with regard to safety and reliability as well as unequivocal technical performance data. The present consensus document is the outcome of an extensive iterative process including ENT specialists, audiologists, health-policy scientists, and representatives/technicians of the main companies in this field. This document should provide a first framework for procedures and technical characterization to enhance effective communication between these stakeholders, improving health care.
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| 32. |
- Shahabi, H Niazi, et al.
(författare)
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Cytochrome P450 2E1 gene polymorphisms/haplotypes and Parkinson's disease in a Swedish population.
- 2009
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Ingår i: Journal of neural transmission (Vienna, Austria : 1996). - : Springer Science and Business Media LLC. - 1435-1463 .- 0300-9564. ; 116:5, s. 567-73
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Tidskriftsartikel (refereegranskat)abstract
- Cytochrome P450 2E1 (CYP2E1), which inter alia is located in dopamine containing neurons in the substantia nigra, has been hypothesized to be of importance for the pathophysiology of Parkinson's disease (PD), either by its production of reactive oxygen species (ROS) or by its capability to detoxify putative neurotoxins. Numerous polymorphisms in the coding and non-coding regions of the gene for this enzyme have been reported. Different variants may account for inter-individual differences in the activity of the enzyme or production of ROS. In this study, the CYP2E1 gene was examined in a control population (n = 272) and a population with PD (n = 347), using a tag-single nucleotide polymorphism (tSNP) approach founded on HapMap Data. Six tSNPs were used in the analysis and haplotype block data were obtained. In case of significance, the SNP was further examined regarding early/late age of disease onset and presence of relatives with PD. We found an association between allele and genotype frequencies of the C/G polymorphism at intron 7 (rs2070676) of this gene and PD (P value of 0.026 and 0.027, respectively). Furthermore, analysis of the rs2070676 polymorphism in subgroups of patients with age of disease onset higher than 50 years and those not having a relative with PD also demonstrated a significant difference with controls. This was seen in both genotype (corresponding to P value = 0.039 and 0.032) and allele (P = 0.027 and 0.017 respectively) frequency. As a representative of many polymorphisms or in possible linkage disequilibrium with other functional variants, it is possible that rs2070676 could influence the regulation of the enzyme. In conclusion, our results display an association between the rs2070676 polymorphism and PD. Additional investigations are needed to elucidate the importance of this polymorphism for the activity of CYP2E1 and PD susceptibility.
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| 33. |
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| 34. |
- Westberg, Lars, 1973, et al.
(författare)
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Association between the estrogen receptor beta gene and age of onset of Parkinson's disease.
- 2004
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Ingår i: Psychoneuroendocrinology. - : Elsevier BV. - 0306-4530. ; 29:8, s. 993-8
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to investigate the potential contribution of genetic variants in the estrogen receptor beta gene to the aetiology of Parkinson's disease (PD). Several lines of evidence from human and animal studies suggest a protective role for estrogen in PD. Recently the estrogen receptor beta subtype was reported to be an important mediator of estrogen actions in the nigrostriatal dopamine system. Two single nucleotide polymorphisms at position 1730 and 1082 in the ER beta gene were genotyped, using pyrosequencing, in 260 patients with PD and 308 controls recruited from the Swedish population. Neither of the two estrogen receptor beta polymorphisms was associated with an increased risk for PD. However, the G allele of the A1730G polymorphism was more frequent in patients with an early age of onset than in patients with a late age of onset of PD (P = 0.006). Patients carrying the GG genotype had an odds ratio of 2.2 for having an early onset of PD compared to non-carriers. In conclusion, our results indicate that genetic variation in the estrogen receptor beta gene may influence the age of onset of PD.
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