| 1. |
- Kilpeläinen, Tuomas O, et al.
(författare)
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Genetic variation near IRS1 associates with reduced adiposity and an impaired metabolic profile.
- 2011
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 43:8, s. 753-60
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies have identified 32 loci influencing body mass index, but this measure does not distinguish lean from fat mass. To identify adiposity loci, we meta-analyzed associations between ∼2.5 million SNPs and body fat percentage from 36,626 individuals and followed up the 14 most significant (P < 10(-6)) independent loci in 39,576 individuals. We confirmed a previously established adiposity locus in FTO (P = 3 × 10(-26)) and identified two new loci associated with body fat percentage, one near IRS1 (P = 4 × 10(-11)) and one near SPRY2 (P = 3 × 10(-8)). Both loci contain genes with potential links to adipocyte physiology. Notably, the body-fat-decreasing allele near IRS1 is associated with decreased IRS1 expression and with an impaired metabolic profile, including an increased visceral to subcutaneous fat ratio, insulin resistance, dyslipidemia, risk of diabetes and coronary artery disease and decreased adiponectin levels. Our findings provide new insights into adiposity and insulin resistance.
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| 2. |
- Kilpeläinen, Tuomas O, et al.
(författare)
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Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P<10(-6) in 19,979 additional individuals. We identify five loci robustly associated (P<5 × 10(-8)) with leptin levels in/near LEP, SLC32A1, GCKR, CCNL1 and FTO. Although the association of the FTO obesity locus with leptin levels is abolished by adjustment for BMI, associations of the four other loci are independent of adiposity. The GCKR locus was found associated with multiple metabolic traits in previous GWAS and the CCNL1 locus with birth weight. Knockdown experiments in mouse adipose tissue explants show convincing evidence for adipogenin, a regulator of adipocyte differentiation, as the novel causal gene in the SLC32A1 locus influencing leptin levels. Our findings provide novel insights into the regulation of leptin production by adipose tissue and open new avenues for examining the influence of variation in leptin levels on adiposity and metabolic health.
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| 3. |
- Sotak, Matus, et al.
(författare)
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Intestinal sodium/glucose cotransporter 3 expression is epithelial and downregulated in obesity.
- 2021
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Ingår i: Life sciences. - : Elsevier BV. - 1879-0631 .- 0024-3205. ; 267
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Tidskriftsartikel (refereegranskat)abstract
- We aimed to determine whether the sodium/glucose cotransporter family member SGLT3, a proposed glucose sensor, is expressed in the intestine and/or kidney, and if its expression is altered in mouse models of obesity and in humans before and after weight-loss surgery.We used in-situ hybridization and quantitative PCR to determine whether the Sglt3 isoforms 3a and 3b were expressed in the intestine and kidney of C57, leptin-deficient ob/ob, and diabetic BTBR ob/ob mice. Western blotting and immunohistochemistry were also used to assess SGLT3 protein levels in jejunal biopsies from obese patients before and after weight-loss Roux-en-Y gastric bypass surgery (RYGB), and in lean healthy controls.Sglt3a/3b mRNA was detected in the small intestine (duodenum, jejunum and ileum), but not in the large intestine or kidneys of mice. Both isoforms were detected in epithelial cells (confirmed using intestinal organoids). Expression of Sglt3a/3b mRNA in duodenum and jejunum was significantly lower in ob/ob and BTBR ob/ob mice than in normal-weight littermates. Jejunal SGLT3 protein levels in aged obese patients before Roux-en-Y gastric bypass (RYGB) were lower than in lean individuals, but substantially upregulated 6months post-RYGB.Our study shows that Sglt3a/3b is expressed primarily in epithelial cells of the small intestine in mice. Furthermore, we observed an association between intestinal mRNA Sglt3a/3b expression and obesity in mice, and between jejunal SGLT3 protein levels and obesity in humans. Further studies are required to determine the possible role of SGLT3 in obesity.
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| 4. |
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| 5. |
- Carlson, Annelie, 1969-, et al.
(författare)
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Energy use due to traffic and pavement maintenance : the cost effectiveness of reducing rolling resistance
- 2016
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- There is a potential to reduce energy use of traffic by performing maintenance measures that lower the rolling resistance. However, the overall aim should be to decrease the total energy use in a life cycle perspective, including energy for both traffic and maintenance. When choosing maintenance alternative, it is also of importance to consider the costs involved. Pavement management is focused on keeping wide spread road networks in acceptable condition given certain budget constraints. Therefore, the economic constraints need to be addressed and in the case of choosing a maintenance alternative that reduces total energy, it also has to be cost-efficient in order for it to be performed. The main scope of the research presented in this report is to investigate how road management should act to reduce total energy use of roads, including traffic and maintenance induced energy use, while also taking cost efficiency and the aspect of uncertainty into consideration. The purpose is to enable a better consideration of the total energy used and maintenance cost when managing the road network. The objective is to derive a meaningful instrument for decision making situations such as when selecting and designing maintenance treatments, in which total energy use and maintenance cost is considered. A general method is developed and presented. A criterion, CR, has been identified for how to choose a pavement maintenance strategy in regards to cost and energy efficiency. A cost benefit analysis approach using Benefit to Cost Ratio, BCR, has been adopted. The study indicates that it is difficult to establish a simple rule of thumb. However, the CR-value may be a useful criterion in some circumstances and it is important to have guidelines as decision support where assessments are made of the road surface characteristics, total energy use and maintenance cost and where the different aspects are valued. This is especially important on an object level.
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| 6. |
- Carswell, Ian, et al.
(författare)
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Main Report on Results of Comparative Site Monitoring
- 2012
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The objective of WP 2 is to analyse the potential use of reclaimed asphalt (RA) in new asphalt surface layer mixes and particularly the use of modified binders. Therefore the chemical compatibility of new binders with old bitumen in RA and the physical performance of the resulting binder and asphalt mixes have been examined separately to develop mix-design guidelines to ensure a long service life of asphalt mixes with reclaimed asphalt.In new bituminous bound courses, especially in base asphalt layers, the use of up to 40 % of RA is state of the art in most of the European countries. In surface layers, RA is currently used in relatively small amounts (10 to 20 %) if at all, because the demands on the properties of surface courses are very high. Surface courses need good deformation resistance at high temperatures as well as a high resistance against top-down cracks at low temperature and good skid resistance. The aggregates and binder used in surface courses are therefore of premium quality.The objective of WP 2 is to analyse the potential use of reclaimed asphalt (RA) in new asphalt surface layer mixes including the use of penetration grade and polymer modified binders (PmB’s). In lower asphalt layers (e.g. bituminous base courses) the use of high quantities of RA is common in most European countries. In surface course layers this occurs less frequently due to the high demands on the surface course.Incorporation of RA into asphalt layers can reduce the demand for added binder to the new mixture, depending on the residual binder content and recovered binder properties of the RA. Using RA in new asphalt mixtures has the potential to reduce costs and reduce energy requirements through reduced demand for raw materials and reduced transport of raw materials. This report covers the performance RA sites monitored which include both plant mixed RA sites (with and without polymer modified binder); and in situ hot recycling sites. The performance of sites is compared with control sections where no RA has been used.
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| 7. |
- Estrada, Karol, et al.
(författare)
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Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture.
- 2012
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 44:5, s. 491-501
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Tidskriftsartikel (refereegranskat)abstract
- Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10(-8)). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 × 10(-4), Bonferroni corrected), of which six reached P < 5 × 10(-8), including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.
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| 8. |
- Karlsson, Robert, 1970-
(författare)
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Investigations of binder rejuvenation related to asphalt recycling
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Investigations described in this doctoral thesis concernmaterial behaviour related to asphalt recycling. More indetail, the thesis describes development and application ofmethods for characterisation of the rejuvenation process, inwhich old and new binders are mixed. The thesis also includes astate-of-the-art report on asphalt recycling focusing onmaterial-related aspects. As the rejuvenation process involves diffusion of bituminousbinders, a method for measuring rate of diffusion based onFTIR-ATR (Fourier Transform Infrared Spectroscopy by AttenuatedTotal Reflectance) was developed. The method was employed forstudying influence of parameters such as temperature, size andshape of the diffusing molecules as well as the viscosity ofthe medium in which the diffusion takes place. Well-definedsubstances, referred to as markers, were used in some of theseinvestigations. By aid of the FTIR-ATR method, influence ofdegree of binder ageing on the rate of diffusion was analysed.Diffusion in bituminous binders was also characterised byrheological measurements. Finally, knowledge on structuralstability of recycled binders was obtained by solubilitystudies using turbidimetric titrations and three differenttitrants showing widely different solubility parameters(iso-octane, isooctanol and methyl-ethyl-ketone). The literature review shows that there are numerouspublications related to asphalt recycling, but fewinvestigations can be characterised as fundamental, whichillustrates the complexity of the research area. The resultspresented show, among other things, that the influence ofdegree of ageing is in principle negligible. A possibleexplanation for this behaviour could be that diffusion takesplace in the maltene phase, which is relatively unaffected byageing. The change in recorded rheological parameterscorrelated fairly well with the rates of diffusion observedusing FTIR-ATR, which indicates that chemical diffusion isaccompanied by changes in binder stiffness. Nothing in theresults presented regarding structural stability of mixtures ofold and new binder suggests that binder stability should be alimiting factor in asphalt recycling, on condition that the oldand new binder are compatible. The doctoral thesis is based onthe following papers, which will be referred to by their Romannumerals: I. Karlsson R., Isacsson U.“Material-Related Aspectsof Asphalt Recycling–State-of-the-art”Submittedfor publication in ASCE J of Transportation Eng. II. Karlsson R., Isacsson U.“Application of FTIR-ATRto Characterisation of Bitumen Rejuvenator Diffusion”Accepted for publ. in ASCE J of Materials in Civil Eng. III. Karlsson R., Isacsson U.“Bitumen RejuvenatorDiffusion as Influenced by Ageing”Int’l J of RoadMaterials and Pavement Design. 3(2) 2002 IV. Karlsson R., Isacsson U.“Laboratory studies ofdiffusion in bitumen using markers”Submitted forpublication in J of Materials Science. V. Karlsson R., Isacsson U., Ekblad J.“RheologicalCharacterisation of Bitumen Diffusion”Submitted forpublication in J of Rheology. VI. Karlsson R., Isacsson U.“Bitumen StructuralStability Characterisation using Turbidimetric Titration”Submitted for publication in Energy and Fuels.
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| 9. |
- Kharrazi, Sogol, 1980-, et al.
(författare)
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Performance based standards for high capacity transports in Sweden : FIFFI project 2013-03881: Report 1: Review of existing regulations and literature
- 2015
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Project Performance Based Standards (PBS) for High Capacity Transports (HCT) in Sweden started at the end of 2013 to investigate applicability of PBS in Sweden. The purpose of the project is to propose a performance based regulation of HCT vehicles and their access to the road network; under a PBS approach to regulation, standards would specify the performance required from vehicle, rather than mandating how this level of performance should be achieved by putting limits on the vehicle length or weight. In this project, all the three domains of safety, infrastructure and environment will be addressed, but the focus is on safety for which extensive testing, simulations and analysis are planned. This report gathers the outcome of work packages 1 and 2 of the project, which is a review of the existing regulation in Sweden, PBS approaches in other countries and relevant literature and regulations.
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| 10. |
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