Laboratory Building

Bergen, Norway

Laboratory Building

Bergen, Norway

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Garcia-Minguillan C.J.,Rovira i Virgili University | Garcia-Minguillan C.J.,CIBER ISCIII | Fernandez-Ballart J.D.,Rovira i Virgili University | Fernandez-Ballart J.D.,CIBER ISCIII | And 12 more authors.
Genes and Nutrition | Year: 2014

Methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR), riboflavin-dependent enzymes, participate in homocysteine metabolism. Reported effects of riboflavin status on the association between the MTHFR 677C>T polymorphism and homocysteine vary, and the effects of the MTRR 66A>G or MTRR 524C>T polymorphisms on homocysteine are unclear. We tested the hypothesis that the effects of the MTHFR 677C>T, MTRR 66A>G and MTRR 524C>T polymorphisms on fasting plasma total homocysteine (tHcy) depend on riboflavin status (erythrocyte glutathionine reductase activation coefficient, optimum: <1.2; marginally deficient: 1.2–1.4; deficient: ≥1.4) in 771 adults aged 18–75 years. MTHFR 677T allele carriers with middle or low tertile plasma folate (<14.7 nmol/L) had 8.2 % higher tHcy compared to the 677CC genotype (p < 0.01). This effect was eliminated when riboflavin status was optimal (p for interaction: 0.048). In the lowest cobalamin quartile (≤273 pmol/L), riboflavin status modifies the relationship between the MTRR 66 A>G polymorphism and tHcy (p for interaction: 0.034). tHcy was 6.6 % higher in MTRR 66G allele carriers compared to the 66AA genotype with marginally deficient or optimal riboflavin status, but there was no difference when riboflavin status was deficient (p for interaction: 0.059). tHcy was 13.7 % higher in MTRR 524T allele carriers compared to the 524CC genotype when cobalamin status was low (p < 0.01), but no difference was observed when we stratified by riboflavin status. The effect of the MTHFR 677C>T polymorphism on tHcy depends on riboflavin status, that of the MTRR 66A>G polymorphism on cobalamin and riboflavin status and that of the MTRR 524C>T polymorphism on cobalamin status. © 2014, Springer-Verlag Berlin Heidelberg.


Yu S.,Jilin University | Wang F.,Jilin University | Wang J.,Jilin University | Chen H.,Jilin University | Chen H.,Laboratory Building
International Journal of Vehicle Design | Year: 2015

This paper establishes a 15 degree-of-freedom (DOF) full-car simulation model for the car Hongqi HQ3. The effectiveness of the model is evaluated by comparison of the real data of HQ3 with the data of the model. Output feedback control of the active suspension is designed based on a half-car model. High quality ride comfort is achieved by minimising the H2 norm from disturbances on the road to the vertical acceleration and the pitch accleration of the car, while safety constraints such as suspension dynamic travels, static/dynamic load ratios and normalised load flows are guaranteed by the generalised H2 norm. The 15 DOF full-car model, together with the left and the right output feedback controllers, form a closed-loop system. The simulation result of the full-car shows that the active suspension can greatly reduce the vertical acceleration, pitch acceleration and roll acceleration as well as satisfy all constraints. Copyright © 2015 Inderscience Enterprises Ltd.


Jung A.Y.,Radboud University Nijmegen | Botma A.,Wageningen University | Lute C.,Wageningen University | Blom H.J.,VU University Amsterdam | And 7 more authors.
Molecular Nutrition and Food Research | Year: 2013

Scope: Low concentrations of folate, other B vitamins, and methionine are associated with colorectal cancer risk, possibly by changing DNA methylation patterns. Here, we examine whether plasma concentrations of B vitamins and methionine are associated with methylation of long interspersed nuclear element-1 (LINE-1) among those at high risk of colorectal cancer, i.e. patients with at least one histologically confirmed colorectal adenoma (CRA) in their life. Methods and results: We used LINE-1 bisulfite pyrosequencing to measure global DNA methylation levels in leukocytes of 281 CRA patients. Multivariable linear regression was used to assess associations between plasma B vitamin concentrations and LINE-1 methylation levels. Plasma folate was inversely associated with LINE-1 methylation in CRA patients, while plasma methionine was positively associated with LINE-1 methylation. Conclusion: This study does not provide evidence that in CRA patients, plasma folate concentrations are positively related to LINE-1 methylation in leukocytes but does suggest a direct association between plasma methionine and LINE-1 methylation in leukocytes. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Colomina J.M.,Rovira i Virgili University | Colomina J.M.,Charles III University of Madrid | Cavalle-Busquets P.,Charles III University of Madrid | Cavalle-Busquets P.,Rovira i Virgili University | And 11 more authors.
Nutrients | Year: 2016

The effect of the betaine: homocysteine methyltransferase BHMT c.716G>A (G: guanosine; A: adenosine) single nucleotide polymorphism (SNP) on the BHMT pathway is unknown during pregnancy. We hypothesised that it impairs betaine to dimethylglycine conversion and that folate status modifies its effect. We studied 612 women from the Reus Tarragona Birth Cohort from ≤12 gestational weeks (GW) throughout pregnancy. The frequency of the variant BHMT c.716A allele was 30.8% (95% confidence interval (CI): 28.3, 33.5). In participants with normal-high plasma folate status (>13.4 nmol/L), least square geometric mean [95% CI] plasma dimethylglycine (pDMG, µmol/L) was lower in the GA (2.35 [2.23, 2.47]) versus GG (2.58 [2.46, 2.70]) genotype at ≤12 GW (p < 0.05) and in the GA (2.08 [1.97, 2.19]) and AA (1.94 [1.75, 2.16]) versus GG (2.29 [2.18, 2.40]) genotypes at 15 GW (p < 0.05). No differences in pDMG between genotypes were observed in participants with possible folate deficiency (≤13.4 µmol/L) (p for interactions at ≤12 GW: 0.023 and 15 GW: 0.038). PDMG was lower in participants with the AA versus GG genotype at 34 GW (2.01 [1.79, 2.25] versus 2.44 [2.16, 2.76] and at labour, 2.51 [2.39, 2.64] versus 3.00 [2.84, 3.18], (p < 0.01)). Possible deficiency compared to normal-high folate status was associated with higher pDMG in multiple linear regression analysis (β coefficients [SEM] ranging from 0.07 [0.04], p < 0.05 to 0.20 [0.04], p < 0.001 in models from early and mid-late pregnancy) and the AA compared to GG genotype was associated with lower pDMG (β coefficients [SEM] ranging from -0.11 [0.06], p = 0.055 to -0.23 [0.06], p < 0.001). Conclusion: During pregnancy, the BHMT pathway is affected by folate status and by the variant BHMT c.716A allele. © 2016 by the authors; licensee MDPI, Basel, Switzerland.


Midttun O.,Laboratory Building | Ueland P.M.,University of Bergen
Rapid Communications in Mass Spectrometry | Year: 2011

We have developed an automated high-throughput assay for the determination of vitamin A (retinol), ergocalciferol (25-OH D2), cholecalciferol (25-OH D3) and vitamin E (α-tocopherol) in a small volume of human plasma. Sample preparation involved mixing 50 μL of plasma with 100 μL of ethanol containing isotope-labelled internal standards, followed by mixing with isooctane/chloroform (3:1, 300 μL). The organic phase was evaporated, and the sample reconstituted in 50 μL methanol. The analysis was performed using reversed-phase liquid chromatography with a gradient mobile phase containing water, methanol and ammonium formate. Chromatographic run-time was 5 min, and positive mode electrospray tandem mass spectrometry (MS/MS) was used for detection. The limits of detection were 0.10 μM for all-trans retinol and 3.3 nM for 25-OH D2 and 25-OH D3. Recoveries were 91.9-105.0%, and within- and between-day coefficients of variance (CVs) 2.4-5.3 and 3.1-8.2, respectively. The assay is presently being used in large-scale studies. Copyright © 2011 John Wiley & Sons, Ltd.


PubMed | Rovira i Virgili University, University of Bergen, Laboratory building and Charles III University of Madrid
Type: Journal Article | Journal: Nutrients | Year: 2016

The effect of the betaine: homocysteine methyltransferase BHMT c.716G>A (G: guanosine; A: adenosine) single nucleotide polymorphism (SNP) on the BHMT pathway is unknown during pregnancy. We hypothesised that it impairs betaine to dimethylglycine conversion and that folate status modifies its effect. We studied 612 women from the Reus Tarragona Birth Cohort from 12 gestational weeks (GW) throughout pregnancy. The frequency of the variant BHMT c.716A allele was 30.8% (95% confidence interval (CI): 28.3, 33.5). In participants with normal-high plasma folate status (>13.4 nmol/L), least square geometric mean [95% CI] plasma dimethylglycine (pDMG, mol/L) was lower in the GA (2.35 [2.23, 2.47]) versus GG (2.58 [2.46, 2.70]) genotype at 12 GW (During pregnancy, the BHMT pathway is affected by folate status and by the variant BHMT c.716A allele.


PubMed | Laboratory Building
Type: Journal Article | Journal: Rapid communications in mass spectrometry : RCM | Year: 2011

We have developed an automated high-throughput assay for the determination of vitamin A (retinol), ergocalciferol (25-OH D2), cholecalciferol (25-OH D3) and vitamin E (-tocopherol) in a small volume of human plasma. Sample preparation involved mixing 50 L of plasma with 100 L of ethanol containing isotope-labelled internal standards, followed by mixing with isooctane/chloroform (3:1, 300 L). The organic phase was evaporated, and the sample reconstituted in 50 L methanol. The analysis was performed using reversed-phase liquid chromatography with a gradient mobile phase containing water, methanol and ammonium formate. Chromatographic run-time was 5 min, and positive mode electrospray tandem mass spectrometry (MS/MS) was used for detection. The limits of detection were 0.10 M for all-trans retinol and 3.3 nM for 25-OH D2 and 25-OH D3. Recoveries were 91.9-105.0%, and within- and between-day coefficients of variance (CVs) 2.4-5.3 and 3.1-8.2, respectively. The assay is presently being used in large-scale studies.

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