| 1. |
- Dominguez, Cecilia A, et al.
(författare)
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Variability in C-type lectin receptors regulates neuropathic pain-like behavior after peripheral nerve injury
- 2014
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Ingår i: Molecular Pain. - : SAGE Publications. - 1744-8069. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Neuropathic pain is believed to be influenced in part by inflammatory processes. In this study we examined the effect of variability in the C-type lectin gene cluster (Aplec) on the development of neuropathic pain-like behavior after ligation of the L5 spinal nerve in the inbred DA and the congenic Aplec strains, which carries seven C-type lectin genes originating from the PVG strain.RESULTS: While both strains displayed neuropathic pain behavior early after injury, the Aplec strain remained sensitive throughout the whole study period. Analyses of several mRNA transcripts revealed that the expression of Interleukin-1β, Substance P and Cathepsin S were more up-regulated in the dorsal part of the spinal cord of Aplec rats compared to DA, indicating a stronger inflammatory response. This notion was supported by flow cytometric analysis revealing increased infiltration of activated macrophages into the spinal cord. In addition, macrophages from the Aplec strain stimulated in vitro displayed higher expression of inflammatory cytokines compared to DA cells. Finally, we bred a recombinant congenic strain (R11R6) comprising only four of the seven Aplec genes, which displayed similar clinical and immune phenotypes as the Aplec strain.CONCLUSION: We here for the first time demonstrate that C-type lectins, a family of innate immune receptors with largely unknown functions in the nervous system, are involved in regulation of inflammation and development of neuropathic pain behavior after nerve injury. Further experimental and clinical studies are needed to dissect the underlying mechanisms more in detail as well as any possible relevance for human conditions.
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| 2. |
- Kiemeney, Lambertus A, et al.
(författare)
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A sequence variant at 4p16.3 confers susceptibility to urinary bladder cancer.
- 2010
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 42:5, s. 415-9
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Tidskriftsartikel (refereegranskat)abstract
- Previously, we reported germline DNA variants associated with risk of urinary bladder cancer (UBC) in Dutch and Icelandic subjects. Here we expanded the Icelandic sample set and tested the top 20 markers from the combined analysis in several European case-control sample sets, with a total of 4,739 cases and 45,549 controls. The T allele of rs798766 on 4p16.3 was found to associate with UBC (odds ratio = 1.24, P = 9.9 x 10(-12)). rs798766 is located in an intron of TACC3, 70 kb from FGFR3, which often harbors activating somatic mutations in low-grade, noninvasive UBC. Notably, rs798766[T] shows stronger association with low-grade and low-stage UBC than with more aggressive forms of the disease and is associated with higher risk of recurrence in low-grade stage Ta tumors. The frequency of rs798766[T] is higher in Ta tumors that carry an activating mutation in FGFR3 than in Ta tumors with wild-type FGFR3. Our results show a link between germline variants, somatic mutations of FGFR3 and risk of UBC.
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| 3. |
- Lindblom, Cecilia, 1979-, et al.
(författare)
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Practical conditions for home and consumer studies in Swedish compulsory education : a survey study
- 2013
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Ingår i: International Journal of Consumer Studies. - : Wiley-Blackwell. - 1470-6423 .- 1470-6431. ; 37:5, s. 556-563
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the study was to map the field of internal and external conditions that Swedish Home and Consumer Studies teachers and pupils have contend with. A questionnaire was constructed and delivered online in November 2010. It contained 27 question covering teacher qualification, quality of premises and equipment, lesson time and collaboration, and the use of national syllabi. A total of 385 persons across the country answered the questionnaire; about 21% of those teaching Home and Consumer Studies in Swedish compulsory school during the school year 2009–2010. These respondents taught in a total of 392 compulsory schools, which equalled about 22% of the schools teaching grades 7–9 in Sweden. Almost a quarter (23%) of the teachers lacked formal training for Home and Consumer Studies. Respondents without an appropriate degree qualification included those trained as nursery school teachers, dietitians and civil engineers. As regards classrooms, while 88% of respondents reported access to fully equipped kitchens with stoves, sinks and work surfaces, 5% used regular classrooms and the remainder were obliged to come up with alternative solutions, such as using portable kitchens in regular classrooms or conducting their lessons in the school restaurant. This study raises many questions about the quality of Home and Consumer Studies provision in a number of schools. The local deficiencies in the nationally decided frame factors for Home and Consumer Studies found by the present study gives us reason to doubt that all pupils achieve the overall learning goals of ‘knowing in practice’ and making informed choices utilizing environmental, economic and health perspectives. This might affect the health and economy of the individuals in the long run, with implications for the national economy and public health. On the basis of these findings, we therefore recommend that current conditions for Home and Consumer Studies and how the subject should operate in schools become a focus for national debate.
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| 4. |
- Lindblom, Rickard P F, et al.
(författare)
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Genetic variability in the rat Aplec C-type lectin gene cluster regulates lymphocyte trafficking and motor neuron survival after traumatic nerve root injury.
- 2013
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Ingår i: Journal of Neuroinflammation. - : Springer Science and Business Media LLC. - 1742-2094. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: C-type lectin (CLEC) receptors are important for initiating and shaping immune responses; however, their role in inflammatory reactions in the central nervous system after traumatic injuries is not known. The antigen-presenting lectin-like receptor gene complex (Aplec) contains a few CLEC genes, which differ genetically among inbred rat strains. It was originally thought to be a region that regulates susceptibility to autoimmune arthritis, autoimmune neuroinflammation and infection.METHODS: The inbred rat strains DA and PVG differ substantially in degree of spinal cord motor neuron death following ventral root avulsion (VRA), which is a reproducible model of localized nerve root injury. A large F2 (DAxPVG) intercross was bred and genotyped after which global expressional profiling was performed on spinal cords from F2 rats subjected to VRA. A congenic strain, Aplec, created by transferring a small PVG segment containing only seven genes, all C-type lectins, ontoDA background, was used for further experiments together with the parental strains.RESULTS: Global expressional profiling of F2 (DAxPVG) spinal cords after VRA and genome-wide eQTL mapping identified a strong cis-regulated difference in the expression of Clec4a3 (Dcir3), a C-type lectin gene that is a part of the Aplec cluster. Second, we demonstrate significantly improved motor neuron survival and also increased T-cell infiltration into the spinal cord of congenic rats carrying Aplec from PVG on DA background compared to the parental DA strain. In vitro studies demonstrate that the Aplec genes are expressed on microglia and upregulated upon inflammatory stimuli. However, there were no differences in expression of general microglial activation markers between Aplec and parental DA rats, suggesting that the Aplec genes are involved in the signaling events rather than the primary activation of microglia occurring upon nerve root injury.CONCLUSIONS: In summary, we demonstrate that a genetic variation in Aplec occurring among inbred strains regulates both survival of axotomized motor neurons and the degree of lymphocyte infiltration. These results demonstrate a hitherto unknown role for CLECs for intercellular communication that occurs after damage to the nervous system, which is relevant for neuronal survival.
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| 5. |
- Lindblom, Rickard P. F., et al.
(författare)
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Unbiased expression mapping identifies a link between the complement and cholinergic systems in the rat central nervous system
- 2014
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Ingår i: Journal of Immunology. - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 192:3, s. 1138-1153
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Tidskriftsartikel (refereegranskat)abstract
- The complement system is activated in a wide spectrum of CNS diseases and is suggested to play a role in degenerative phenomena such as elimination of synaptic terminals. Still, little is known of mechanisms regulating complement activation in the CNS. Loss of synaptic terminals in the spinal cord after an experimental nerve injury is increased in the inbred DA strain compared with the PVG strain and is associated with expression of the upstream complement components C1q and C3, in the absence of membrane attack complex activation and neutrophil infiltration. To further dissect pathways regulating complement expression, we performed genome-wide expression profiling and linkage analysis in a large F2(DA × PVG) intercross, which identified quantitative trait loci regulating expression of C1qa, C1qb, C3, and C9. Unlike C1qa, C1qb, and C9, which all displayed distinct coregulation with different cis-regulated C-type lectins, C3 was regulated in a coexpression network immediately downstream of butyrylcholinesterase. Butyrylcholinesterase hydrolyses acetylcholine, which exerts immunoregulatory effects partly through TNF-α pathways. Accordingly, increased C3, but not C1q, expression was demonstrated in rat and mouse glia following TNF-α stimulation, which was abrogated in a dose-dependent manner by acetylcholine. These findings demonstrate new pathways regulating CNS complement expression using unbiased mapping in an experimental in vivo system. A direct link between cholinergic activity and complement activation is supported by in vitro experiments. The identification of distinct pathways subjected to regulation by naturally occurring genetic variability is of relevance for the understanding of disease mechanisms in neurologic conditions characterized by neuronal injury and complement activation.
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| 6. |
- Lönnqvist, Tomas, 1979-, et al.
(författare)
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The potential for waste to biogas in La Paz and El Alto in Bolivia
- 2013
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Ingår i: 1st International Water Association Conference on HolisticSludge Management, 2013, Västerås Sweden.
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Konferensbidrag (refereegranskat)abstract
- In the cities of La Paz and El Alto, 573 tons of organic material are disposed in landfills every day. These residues can be used to produce biogas and recycle nutrients, thus alleviating environmental impacts related to waste management. Technical solutions are evaluated through a multicriteria analysis with the purpose of defining a strategy for implementing waste-to-biogas in the two cities. As a result, the development for waste-to-biogas-system is defined in three steps. Step 1 consists of an active extraction system of landfill gas in the already existing landfills. Step 2 implies the establishment of a dry-digestion biogas facility based on present waste collection practices, that is, not segregated waste. Step 3 consists of a biogas plant using dry digestion for processing source segregated bio-waste. The economic feasibility of these three steps is evaluated. Despite prevailing fossil fuels subsidies in the country, implementing waste-to-biogas turn out feasible in the country provided the digestate is commercialized as bio-fertilizer or erosion control material and additional services such as waste collection and deposition are computed in the total economy of the biogas production plant.
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| 7. |
- Rafnar, Thorunn, et al.
(författare)
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European genome-wide association study identifies SLC14A1 as a new urinary bladder cancer susceptibility gene.
- 2011
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Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 0964-6906. ; 20:21, s. 4268-81
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Tidskriftsartikel (refereegranskat)abstract
- Three genome-wide association studies in Europe and the USA have reported eight urinary bladder cancer (UBC) susceptibility loci. Using extended case and control series and 1000 Genomes imputations of 5 340 737 single-nucleotide polymorphisms (SNPs), we searched for additional loci in the European GWAS. The discovery sample set consisted of 1631 cases and 3822 controls from the Netherlands and 603 cases and 37 781 controls from Iceland. For follow-up, we used 3790 cases and 7507 controls from 13 sample sets of European and Iranian ancestry. Based on the discovery analysis, we followed up signals in the urea transporter (UT) gene SLC14A. The strongest signal at this locus was represented by a SNP in intron 3, rs17674580, that reached genome-wide significance in the overall analysis of the discovery and follow-up groups: odds ratio = 1.17, P = 7.6 × 10(-11). SLC14A1 codes for UTs that define the Kidd blood group and are crucial for the maintenance of a constant urea concentration gradient in the renal medulla and, through this, the kidney's ability to concentrate urine. It is speculated that rs17674580, or other sequence variants in LD with it, indirectly modifies UBC risk by affecting urine production. If confirmed, this would support the 'urogenous contact hypothesis' that urine production and voiding frequency modify the risk of UBC.
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