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| 2. |
- Aulchenko, Yurii S, et al.
(författare)
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Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts
- 2009
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 41:1, s. 47-55
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Tidskriftsartikel (refereegranskat)abstract
- Recent genome-wide association (GWA) studies of lipids have been conducted in samples ascertained for other phenotypes, particularly diabetes. Here we report the first GWA analysis of loci affecting total cholesterol (TC), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglycerides sampled randomly from 16 population-based cohorts and genotyped using mainly the Illumina HumanHap300-Duo platform. Our study included a total of 17,797-22,562 persons, aged 18-104 years and from geographic regions spanning from the Nordic countries to Southern Europe. We established 22 loci associated with serum lipid levels at a genome-wide significance level (P < 5 x 10(-8)), including 16 loci that were identified by previous GWA studies. The six newly identified loci in our cohort samples are ABCG5 (TC, P = 1.5 x 10(-11); LDL, P = 2.6 x 10(-10)), TMEM57 (TC, P = 5.4 x 10(-10)), CTCF-PRMT8 region (HDL, P = 8.3 x 10(-16)), DNAH11 (LDL, P = 6.1 x 10(-9)), FADS3-FADS2 (TC, P = 1.5 x 10(-10); LDL, P = 4.4 x 10(-13)) and MADD-FOLH1 region (HDL, P = 6 x 10(-11)). For three loci, effect sizes differed significantly by sex. Genetic risk scores based on lipid loci explain up to 4.8% of variation in lipids and were also associated with increased intima media thickness (P = 0.001) and coronary heart disease incidence (P = 0.04). The genetic risk score improves the screening of high-risk groups of dyslipidemia over classical risk factors.
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- Heard-Costa, Nancy L, et al.
(författare)
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NRXN3 is a novel locus for waist circumference : a genome-wide association study from the CHARGE Consortium
- 2009
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Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 5:6, s. e1000539-
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Tidskriftsartikel (refereegranskat)abstract
- Central abdominal fat is a strong risk factor for diabetes and cardiovascular disease. To identify common variants influencing central abdominal fat, we conducted a two-stage genome-wide association analysis for waist circumference (WC). In total, three loci reached genome-wide significance. In stage 1, 31,373 individuals of Caucasian descent from eight cohort studies confirmed the role of FTO and MC4R and identified one novel locus associated with WC in the neurexin 3 gene [NRXN3 (rs10146997, p = 6.4×10−7)]. The association with NRXN3 was confirmed in stage 2 by combining stage 1 results with those from 38,641 participants in the GIANT consortium (p = 0.009 in GIANT only, p = 5.3×10−8 for combined analysis, n = 70,014). Mean WC increase per copy of the G allele was 0.0498 z-score units (0.65 cm). This SNP was also associated with body mass index (BMI) [p = 7.4×10−6, 0.024 z-score units (0.10 kg/m2) per copy of the G allele] and the risk of obesity (odds ratio 1.13, 95% CI 1.07–1.19; p = 3.2×10−5 per copy of the G allele). The NRXN3 gene has been previously implicated in addiction and reward behavior, lending further evidence that common forms of obesity may be a central nervous system-mediated disorder. Our findings establish that common variants in NRXN3 are associated with WC, BMI, and obesity.
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| 4. |
- Herman, Maria Dolores, et al.
(författare)
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Structures of BIR domains from human NAIP and cIAP2
- 2009
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Ingår i: Acta Crystallographica. Section F. - 1744-3091 .- 1744-3091. ; 65, s. 1091-1096
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Tidskriftsartikel (refereegranskat)abstract
- The inhibitor of apoptosis (IAP) family of proteins contains key modulators of apoptosis and inflammation that interact with caspases through baculovirus IAP-repeat (BIR) domains. Overexpression of IAP proteins frequently occurs in cancer cells, thus counteracting the activated apoptotic program. The IAP proteins have therefore emerged as promising targets for cancer therapy. In this work, X-ray crystallography was used to determine the first structures of BIR domains from human NAIP and cIAP2. Both structures harbour an N-terminal tetrapeptide in the conserved peptide-binding groove. The structures reveal that these two proteins bind the tetrapeptides in a similar mode as do other BIR domains. Detailed interactions are described for the P1'-P4' side chains of the peptide, providing a structural basis for peptide-specific recognition. An arginine side chain in the P3' position reveals favourable interactions with its hydrophobic moiety in the binding pocket, while hydrophobic residues in the P2' and P4' pockets make similar interactions to those seen in other BIR domain-peptide complexes. The structures also reveal how a serine in the P1' position is accommodated in the binding pockets of NAIP and cIAP2. In addition to shedding light on the specificity determinants of these two proteins, the structures should now also provide a framework for future structure-based work targeting these proteins.
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| 5. |
- Holmberg, Christin, et al.
(författare)
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Vägen till arbete : Uppföljningsstudie av studenter med examen vid Växjö universitet
- 2005
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Under 2004 påbörjades studien Vägen till arbete som är en fortsättningpå de studentundersökningar som startades vid Växjö universitet1999. Studien syftar till att få större kunskaper om alumners(före detta studenter) väg ut i arbetslivet efter examen, hur de värderar sin utbildning idag och hur de uppfattar sin möjlighet till anställning.En högskoleutbildning leder inte automatiskt till ett arbete,utan andra faktorer påverkar alumnernas anställningsbarhet, såsomutbildning, yrkes-, arbetslivserfarenhet, yrkesidentitet och kontaktnät.Undersökningen visar hur alumnerna försökte ta sig in på arbetsmarknaden genom att påverka dessa faktorer.För att få ytterligare ett perspektiv på alumnernas möjlighet till anställning genomfördes intervjuer med rekryterare på olika företagoch myndigheter. Därigenom skapar rekryterarnas syn på anställningsbarhet en bredare förståelse för den verklighet alumnerna möter i vägen till arbete. Rekryterarna tog upp samma faktorer somalumnerna, men de inkluderade även specifika egenskaper/färdigheteroch social kompetens.I undersökningen studeras även hur alumnernas väg till arbete kanunderlättas. Både alumnerna och rekryterarna menade att en ökadkontakt med arbetslivet under studietiden förbättrar möjligheternatill anställning. En ökad kontakt leder till bättre kunskap om hurarbetslivet fungerar och förståelse för vilka framtida arbeten somutbildningen kan leda fram till. Därför föreslog alumnerna och rekryterarna mer praktik, studiebesök, gästföreläsningar, examensarbete/uppsatsarbete, mentorskap och skapandet av tydligare yrkesidentitet, vilka skulle kunna utföras genom en alumnverksamhet. Den innebär att det finns ett utbyte mellan arbetsliv, alumner och universitet.Alumnerna utgör en viktig resurs i samverkansarbetet eftersom dekan vara länken mellan universitetet och arbetslivet.Undersökningen består av tre delar och den första är en enkätstudieav alumner som tog examen vid Växjö universitet läsåret 2000/2001.Genom den belyses till exempel alumnernas bakgrund och derasarbetssituation. Andra delen utgörs av en intervjustudie med alumnersom är bosatta i Växjö, Malmö och Stockholm, vilken ger en bild avalumnernas inträde på arbetsmarkanden efter examen. Tredje deleni undersökningen består av en intervjustudie med rekryterare från olikamyndigheter och företag i Kronobergs län, Malmö och Stockholm.
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| 6. |
- Johansson, Ulrika, 1974-, et al.
(författare)
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Formation of composite endothelial cell-mesenchymal stem cell islets : a novel approach to promote islet revascularization
- 2008
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 57:9, s. 2393-2401
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Mesenchymal stem cells (MSCs) contribute to endothelial cell (EC) migration by producing proteases, thereby paving the way into the tissues for ECs. MSCs were added to our previously described composite EC islets as a potential means to improve their capacity for islet angiogenesis. RESEARCH DESIGN AND METHODS: Human islets were coated with primary human bone marrow-derived MSCs and dermal microvascular ECs. The capacity of ECs, with or without MSCs, to adhere to and grow into human islets was analyzed. The survival and functionality of these composite islets were evaluated in a dynamic perifusion assay, and their capacity for angiogenesis in vitro was assessed in a three-dimensional fibrin gel assay. RESULTS: ECs proliferated after culture in MSC-conditioned medium, and MSCs improved the EC coverage threefold compared with EC islets alone. Islet survival in vitro and the functionality of the composite islets after culture were equal to those of control islets. The EC-MSC islets showed a twofold increase in total sprout formation compared with EC islets, and vascular sprouts emanating from the EC-MSC-islet surface showed migration of ECs into the islets and also into the surrounding matrix, either alone or in concert with MSCs. CONCLUSIONS: EC proliferation, sprout formation, and ingrowth of ECs into the islets were enhanced by MSCs. The use of composite EC-MSC islets may have beneficial effects on revascularization and immune regulation. The technique presented allows for pretreatment of donor islets with recipient-derived ECs and MSCs as a means of improving islet engraftment.
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| 7. |
- Johnsson, Richard, et al.
(författare)
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Reductive openings of benzylidene acetals. Kinetic studies of borane and alane activation by Lewis acids.
- 2008
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Ingår i: Carbohydrate Research. - : Elsevier BV. - 1873-426X .- 0008-6215. ; 343, s. 2997-3000
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Tidskriftsartikel (refereegranskat)abstract
- The reaction kinetics for a number of reductive openings of methyl 2,3-di-O-benzyl-4,6-O-benzylidene-alpha-d-glucopyranoside have been investigated. Openings to give free HO-6 (using BH(3).THF-AlCl(3)-THF or LiAlH(4)-AlCl(3)-Et(2)O) follow first order kinetics, while reactions yielding free HO-4 (using BH(3).NMe(3)-AlCl(3)-THF or BH(3).NMe(3)-BF(3).OEt(2)-THF) follow higher order kinetics. The addition of water to the BH(3).NMe(3)-AlCl(3)-THF results in faster reactions. The BH(3).SMe(2)-AlCl(3)-THF system constitutes a borderline case, yielding both free HO-6 (by a first order reaction) and free HO-4 (by a higher order reaction). These results correlate well with the concept of regioselectivity by activation of borane complexes.
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| 8. |
- Lindman, Stina, et al.
(författare)
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Green fluorescence induced by EF-hand assembly in a split GFP system.
- 2009
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Ingår i: Protein Science. - : Wiley. - 1469-896X .- 0961-8368. ; 18:6, s. 1221-1229
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Tidskriftsartikel (refereegranskat)abstract
- The affinity between the 1-157 and 158-238 fragments of green fluorescent protein (GFP) is too low for spontaneous in vivo reassembly of the protein upon co-expression of the two fragments. This prevents chromophore maturation and the cells lack GFP fluorescence. We have utilized the very high affinity between the two EF-hands of calbindin D(9k) to facilitate GFP assembly from its fragments and to introduce a calcium dependent molecular switch. In GFPN-EF1, residues 1-157 of GFP are fused to residues 1-43 of calbindin, and in EF2-GFPC, residues 44-75 of calbindin are fused to residues 158-238 of GFP. When co-expressed, GFPN-EF1 and EF2-GFPC associate spontaneously and rapidly resulting in a folded reconstituted protein with bright GFP fluorescence. The high affinity of GFPN-EF1 for EF2-GFPC leads to brighter fluorescence of the cells compared to cells with a control constructs carrying leucine zippers (Wilson et al., Nature Methods 2004;3:255). The complex of GFPN-EF1 and EF2-GFPC was purified from cells using metal-ion chelate chromatography and the temperature dependence of GFP fluorescence was found to be calcium dependent. The GFPN-EF1 and EF2-GFPC fragments were separated by ion exchange chromatography. The assembly of the fragments was found to be reversible and the complex was regained upon mixing, as evidenced by surface plasmon resonance (SPR) data. The affinity between GFPN-EF1 and EF2-GFPC as well as rates of association and dissociation were found to be Ca(2+)-dependent.
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| 9. |
- Pettersson, Anna, et al.
(författare)
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Near Real-Time Standoff Detection of Explosives in a Realistic Outdoor Environment at 55 m Distance
- 2009
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Ingår i: Propellants, Explosives, Pyrotechnics. - : Wiley. - 1521-4087 .- 0721-3115. ; 34:4, s. 297-306
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Tidskriftsartikel (refereegranskat)abstract
- Standoff identification of explosives at distances of up to 55 in has been performed by applying spontaneous Raman spectroscopy. This work has been focused on detection in a realistic environment, using an outdoors test field and performing experiments under varying weather conditions such as rain- or snowfall or bright sunshine. The instrumentation, based on a 532 nm pulsed laser source combined with gated detection, proved the performance insensitive to weather variations. Investigated HMEs and precursors were TATP, HMTD, HP, MEKP, NM, NB, and IPN; all in bulk quantities. The time needed for acquiring spectra was typically between single pulse (5 ns) and 10 s. Detection through green and brown glass bottles and PET bottles were tried and found viable.
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