| 1. |
- Thorgeirsson, Thorgeir E, et al.
(författare)
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A variant associated with nicotine dependence, lung cancer and peripheral arterial disease
- 2008
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 452:7187, s. 9-638
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Tidskriftsartikel (refereegranskat)abstract
- Smoking is a leading cause of preventable death, causing about 5 million premature deaths worldwide each year(1,2). Evidence for genetic influence on smoking behaviour and nicotine dependence (ND)(3-8) has prompted a search for susceptibility genes. Furthermore, assessing the impact of sequence variants on smoking-related diseases is important to public health(9,10). Smoking is the major risk factor for lung cancer (LC)(11-14) and is one of the main risk factors for peripheral arterial disease (PAD)(15-17). Here we identify a common variant in the nicotinic acetylcholine receptor gene cluster on chromosome 15q24 with an effect on smoking quantity, ND and the risk of two smoking- related diseases in populations of European descent. The variant has an effect on the number of cigarettes smoked per day in our sample of smokers. The same variant was associated with ND in a previous genomewide association study that used low- quantity smokers as controls(18,19), and with a similar approach we observe a highly significant association with ND. A comparison of cases of LC and PAD with population controls each showed that the variant confers risk of LC and PAD. The findings provide a case study of a gene - environment interaction(20), highlighting the role of nicotine addiction in the pathology of other serious diseases.
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| 2. |
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| 3. |
- Liu, Xiao Li, et al.
(författare)
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Characterization of the interactions of the nephrin intracellular domain
- 2005
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Ingår i: The FEBS Journal. - : Wiley. - 1742-464X .- 1742-4658. ; 272:1, s. 228-243
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Tidskriftsartikel (refereegranskat)abstract
- Nephrin is a signalling cell-cell adhesion protein of the Ig superfamily and the first identified component of the slit diaphragm that forms the critical and ultimate part of the glomerular ultrafiltration barrier. The extracellular domains of the nephrin molecules form a network of homophilic and heterophilic interactions building the structural scaffold of the slit diaphragm between the podocyte foot processes. The intracellular domain of nephrin is connected indirectly to the actin cytoskeleton, is tyrosine phosphorylated, and mediates signalling from the slit diaphragm into the podocytes. CD2AP, podocin, Fyn kinase, and phosphoinositide 3-kinase are reported intracellular interacting partners of nephrin, although the biological roles of these interactions are unclarified. To characterize the structural properties and protein-protein interactions of the nephrin intracellular domain, we produced a series of recombinant nephrin proteins. These were able to bind all previously identified ligands, although the interaction with CD2AP appeared to be of extremely low stoichiometry. Fyn phosphorylated nephrin proteins efficiently in vitro. This phosphorylation was required for the binding of phosphoinositide 3-kinase, and significantly enhanced binding of Fyn itself. A protein of 190 kDa was found to associate with the immobilized glutathione S-transferase-nephrin. Peptide mass fingerprinting and amino acid sequencing identified this protein as IQGAP1, an effector protein of small GTPases Rac1 and Cdc42 and a putative regulator of cell-cell adherens junctions. IQGAP1 is expressed in podocytes at significant levels, and could be found at the immediate vicinity of the slit diaphragm. However, further studies are needed to confirm the biological significance of this interaction and its occurrence in vivo.
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| 4. |
- Nordqvist, A., et al.
(författare)
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Characterisation of metal droplets sampled during top lance blowing
- 2009
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Ingår i: Ironmaking & steelmaking. - : Informa UK Limited. - 0301-9233 .- 1743-2812. ; 36:6, s. 421-431
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Tidskriftsartikel (refereegranskat)abstract
- Laboratory trials were performed in an induction furnace to study droplet formation during lance blowing. Oxygen was blown on a molten iron bath consisting of iron alloyed with carbon and silicon. Iron droplets were collected using a specially designed sampler. The average iron droplet composition and the oxide layer thickness were determined using scanning electron microscopy combined with energy dispersed spectroscopy. In addition, the concentration gradient of elements was determined using electron probe microanalysis. It should be noted that a special technique had to be developed in order to prepare the droplet sample. The size distribution and composition of the droplets were also determined using the microprobe. The carbon was found to be homogeneously distributed throughout the droplet independently of the size of the droplet. For the experiments using both carbon and silicon it was found that the silicon in most droplets could be found in the periphery of the droplets. It was also found that the tendency was that both the carbon content as well as the silicon content in the droplets decreased with a decreased droplet size. Thus, it was concluded that it is necessary to modify top blown decarburisation processes so that a maximum area between droplet and atmosphere is obtained.
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| 5. |
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| 6. |
- Svensson, Johan, 1964, et al.
(författare)
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Growth hormone (GH) replacement therapy in GH deficient adults: predictors of one-year metabolic and clinical response.
- 2007
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Ingår i: Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society. - : Elsevier BV. - 1096-6374 .- 1532-2238. ; 17:1, s. 67-76
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: This study investigated whether baseline status could predict the responsiveness to one-year growth hormone (GH) replacement therapy in adult GH deficient (GHD) patients. DESIGN: A total of 380 European patients with adult onset GHD due to non-functioning pituitary adenoma that had been enrolled in Pfizer International Metabolic Database (KIMS), and that had completed one year of GH replacement therapy within KIMS, were studied. RESULTS: The mean initial dose of GH was 0.22 (SEM 0.01) mg/day and after one year, the mean dose was 0.36 (0.01) mg/day. The mean insulin-like growth factor-I (IGF-I) SD score increased from -1.75 (0.08) at baseline to 0.47 (0.05) after one year. Quality of life (QoL)-Assessment of GHD in Adults (QoL-AGHDA), waist circumference, waist:hip ratio, and serum lipid pattern improved. Women received a higher dose of GH than men after one year, and demonstrated similar treatment response. In multiple stepwise forward regression analyses, the one-year changes in QoL-AGHDA score, waist:hip ratio, and serum low density lipoprotein-cholesterol (LDL-C) level correlated inversely with the baseline values of the same variable. In addition, the change after one year in QoL-AGHDA score correlated inversely with duration of hypopituitarism and baseline serum high density lipoprotein-cholesterol (HDL-C) level, and the change in waist:hip ratio correlated inversely, although more weakly, with baseline serum HDL-C level and UK citizenship and positively with baseline waist circumference and the initial GH dose. The change in serum LDL-C level additionally correlated inversely with the mean GH dose and duration of hypopituitarism and positively with UK citizenship. CONCLUSIONS: Baseline status could, with moderate strength, predict the responsiveness in the same variable whereas it could not, or only weakly, predict the response in other variables. Therefore, when the decision to start GH replacement is undertaken, as many outcome variables as possible should be evaluated in order to adequately evaluate the likelihood of clinical benefit. Finally, women have a similar response to GH replacement as men when individualised GH dosing schedules are employed and should therefore be selected for GH therapy to a similar extent.
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| 7. |
- Östberg, Tomas L., et al.
(författare)
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Accelerated biodegradation of n-alkanes in aqueous solution by the addition of fermented whey
- 2006
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Ingår i: International Biodeterioration & Biodegradation. - : Elsevier BV. - 0964-8305 .- 1879-0208. ; 57:3, s. 190-194
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Tidskriftsartikel (refereegranskat)abstract
- The effect of fermented whey on the aerobic degradation of n-alkanes by a microbial consortium was investigated in an aqueous system. Microbial degradation of 100 mg n-alkanes (C12, C14, C16 and C18) in mineral nutrient medium was assessed by measuring the decrease in n-alkanes, production of CO2 and increase in biomass. The addition of fermented whey at a concentration of 5 mg dry weight to a nutrient medium receiving a small-sized inoculum (103.4 CFU ml-1)shortened the lag phase from 8 to 3 days, but the degradation rate during the degradation phase was not enhanced. The shortened lag phase at low initial concentration of microorganisms indicates that the fermented whey stimulates growth in the initial phase, without reducing the consortium's capacity for n-alkane degradation.
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