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| 2. |
- Bao, Ling, 1980, et al.
(författare)
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U-Duality and the Compactified Gauss-Bonnet Term
- 2007
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Ingår i: Journal of High Energy Physics.
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Tidskriftsartikel (refereegranskat)abstract
- We present the complete toroidal compactification of the Gauss-Bonnet Lagrangian from D dimensions to D-n dimensions. Our goal is to investigate the resulting action from the point of view of the "U-duality" symmetry SL(n+1,R) which is present in the tree-level Lagrangian when D-n=3. The analysis builds upon and extends the investigation of the paper [arXiv:0706.1183], by computing in detail the full structure of the compactified Gauss-Bonnet term, including the contribution from the dilaton exponents. We analyze these exponents using the representation theory of the Lie algebra sl(n+1,R) and determine which representation is the relevant one for quadratic curvature corrections. By interpreting the result of the compactification as a leading term in a large volume expansion of an SL(n+1,Z)-invariant action, we conclude that the overall exponential dilaton factor should not be included in the representation structure. As a consequence, all dilaton exponents correspond to weights of sl(n+1,R), which, nevertheless, remain on the positive side of the root lattice.
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| 4. |
- Carlsson, Per-Anders, 1972, et al.
(författare)
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Periodic control for improved low-temperature catalytic activity
- 2001
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Ingår i: Topics in Catalysis. - 1572-9028 .- 1022-5528. ; 16-17:1-4, s. 343-347
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Tidskriftsartikel (refereegranskat)abstract
- The influence of transient changes in the gas composition on the low-temperature activity of a commercial three-way catalyst and a Pt/Al2O3 model catalyst has been studied. By introducing well-controlled periodic O2 pulses to simple gas mixtures of CO or C3H6 (in N2), a substantial improvement of the low temperature oxidation activity was observed for both catalysts. The reason for low activity at low temperatures is normally attributed to self-poisoning by CO or hydrocarbons. The improved catalytic performance observed here is suggested to origin from the transients causing a surface reactant composition that is favourable for the reaction rate.
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| 5. |
- Hedlund, Joel, 1978-, et al.
(författare)
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Analysis of ancient sequence motifs in the H+ -PPase family
- 2006
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Ingår i: The FEBS Journal. - : Wiley. - 1742-464X .- 1742-4658. ; 273, s. 5183-5193
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Tidskriftsartikel (refereegranskat)abstract
- The unique family of membrane-bound proton-pumping inorganic pyrophosphatases, involving pyrophosphate as the alternative to ATP, was investigated by characterizing 166 members of the UniProtKB ⁄ Swiss-Prot + UniProtKB ⁄TrEMBL databases and available completed genomes, using sequence comparisons and a hidden Markov model based upon a conserved 57-residue region in the loop between transmembrane segments 5 and 6. The hidden Markov model was also used to search the approximately one million sequences recently reported from a large-scale sequencing project of organisms in the Sargasso Sea, resulting in additional 164 partial pyrophosphatase sequences. The strongly conserved 57-residue region was found to contain two nonapeptidyl sequences, mainly consisting of the four ‘very early’ proteinaceous amino acid residues Gly, Ala, Val and Asp, compatible with an ancient origin of the inorganic pyrophosphatases. The nonapeptide patterns have charged amino acid residues at positions 1, 5 and 9, are apparent binding sites for the substrate and parts of the active site, and were shown to be so specific for these enzymes that they can be used for functional assignments of unannotated genomes.
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| 6. |
- Hellgren, Mikko, 1972-, et al.
(författare)
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Alcohol dehydrogenase 2 is a major hepatic enzyme for human retinol metabolism
- 2007
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Ingår i: Cellular and Molecular Life Sciences (CMLS). - : Springer. - 1420-682X .- 1420-9071. ; 64:4, s. 498-505
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Tidskriftsartikel (refereegranskat)abstract
- The metabolism of all-trans- and 9-cis-retinol/ retinaldehyde has been investigated with focus on the activities of human, mouse and rat alcohol dehydrogenase 2 (ADH2), an intriguing enzyme with apparently different functions in human and rodents. Kinetic constants were determined with an HPLC method and a structural approach was implemented by in silico substrate dockings. For human ADH2, the determined K(m) values ranged from 0.05 to 0.3 microM and k(cat) values from 2.3 to 17.6 min(-1), while the catalytic efficiency for 9-cis-retinol showed the highest value for any substrate. In contrast, poor activities were detected for the rodent enzymes. A mouse ADH2 mutant (ADH2Pro47His) was studied that resembles the human ADH2 setup. This mutation increased the retinoid activity up to 100-fold. The K(m) values of human ADH2 are the lowest among all known human retinol dehydrogenases, which clearly support a role in hepatic retinol oxidation at physiological concentrations.
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| 7. |
- Henriksson, M., et al.
(författare)
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Separate functional features of proinsulin C-peptide
- 2005
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Ingår i: Cellular and Molecular Life Sciences (CMLS). - : Springer Science and Business Media LLC. - 1420-682X .- 1420-9071. ; 62:15, s. 1772-1778
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Tidskriftsartikel (refereegranskat)abstract
- Proinsulin C-peptide influences a number of physiological parameters in addition to its well-established role in the parent proinsulin molecule. It is of interest as a candidate for future co-replacement therapy with insulin for patients with diabetes mellitus type 1, but specific receptors have not been identified and additional correlation with functional effects is desirable. Based on comparisons of 22 mammalian proinsulin variants, we have constructed analogues for activity studies, choosing phosphorylation of mitogen-activated protein kinases (MAPKs) in Swiss 3T3 fibroblasts for functional measurements. In this manner, we find that effective phosphorylation of MAPKs is promoted by the presence of conserved glutamic acid residues at positions 3, 11 and 27 of C-peptide and by the presence of helix-promoting residues in the N-terminal segment. Previous findings have ascribed functional roles to the C-terminal pentapeptide segment, and all results combined therefore now show the importance of different segments, suggesting that C-peptide interactions are complex or multiple. © Birkhäuser Verlag, 2005.
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| 8. |
- Jansson, Agneta, 1973-, et al.
(författare)
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A new polymorphism in the coding region of exon four in HSD17B2 in relation to risk of sporadic and hereditary breast cancer
- 2007
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Ingår i: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 0167-6806 .- 1573-7217. ; 106:1, s. 57-64
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Tidskriftsartikel (refereegranskat)abstract
- In situ synthesis of oestrogens is of great importance in the development and progression of breast cancer. 17β-hydroxysteroid dehydrogenase (17HSD) type 2 catalyses oxidation from oestradiol to oestrone, and thereby protects the breast epithelial cells from oestradiol. Low expression of 17HSD type 2 has been associated with decreased survival in breast cancer, but no studies have investigated the mechanism behind the low expression. The 17HSD type 2 gene (HSD17B2) was screened for mutations with Single Stranded Conformation Polymorphism (SSCP)-DNA sequencing in 59 sporadic breast cancer cases, 19 hereditary breast cancer cases and seven breast cancer cell lines. DNA samples from 226 healthy individuals were used to identify if changes were previously unknown polymorphisms. No mutation was detected and therefore mutations in HSD17B2 do not explain why some breast tumours exhibit low 17HSD type 2 expression. However, a previously unknown polymorphism was found in exon four (Met226Val). Using molecular modelling, we found that the substituted residue is located at the outer part of the steroid binding site, probably causing minor alterations in the substrate binding. We further studied if the polymorphism contributes to breast cancer susceptibility in a larger material, but did not find an increased risk in the group of 317 sporadic breast cancer patients, 188 breast cancer patients with two close relatives with breast cancer or 122 hereditary breast cancer patients, compared to the healthy control group. We suggest that the detected polymorphism does not contribute to a higher risk of developing breast cancer.
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| 11. |
- Lavebratt, C., et al.
(författare)
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Association study between chromosome 10q26.11 and obesity among Swedish men
- 2005
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Ingår i: International Journal of Obesity. - : Springer Science and Business Media LLC. - 0307-0565 .- 1476-5497. ; 29:12, s. 1422-1428
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Proximal chromosome 10q26 was recently linked to waist/hip ratio in European and African-American families. The objective was to investigate whether genomic variation in chromosome 10q26.11 reflects variation in obesity-related clinical parameters in a Swedish population. DESIGN: Genetic association study of single-nucleotide polymorphisms (SNPs) in chromosome 10q26.11 and obesity-related clinical parameters was performed. Obesity was defined as body mass index (BMI)≥30 kg/m2. SUBJECTS: Swedish Caucasians comprising 276 obese and 480 nonobese men, 313 obese and 494 nonobese women, 177 obese and 163 nonobese patients with type 2 diabetes mellitus (T2DM), and 106 obese and 201 nonobese subjects with impaired glucose tolerance (IGT) patients. MEASUREMENTS: Genotypes of 11 SNPs at chromosome 10q26.11, and various obesity-related clinical parameters. RESULTS: Homozygosity of a common haplotype constructed by three SNPs, rs2185937, rs1797 and hCV1402327, covering an interval of 2.7 kb, was suggested to confer an increased risk for obesity of 1.5 among men (P=0.043). The C allele frequency and homozygous genotype frequency of the rs1797 tended to be higher among obese compared to among nonobese men (P=0.017 and 0.020, respectively). The distribution of BMI and diastolic blood pressure was higher among those with the C/C genotype (P=0.022 and 0.0061, respectively). The obese and the nonobese groups were homogeneous over BMI subgroups with regard to rs1797 risk genotype distribution. There was no tendency for association between rs1797 and obesity among neither women nor T2DM nor IGT patients. CONCLUSION: We show support for association between proximal chromosome 10q26.11 and obesity among Swedish men but not women through the analysis of a haplotype encompassing 2.7 kb. © 2005 Nature Publishing Group All rights reserved.
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| 15. |
- Okamoto, H., et al.
(författare)
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Mutation analysis of the human 5-lipoxygenase C-terminus : Support for a stabilizing C-terminal loop
- 2005
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Ingår i: Biochimica et Biophysica Acta - Proteins and Proteomics. - : Elsevier BV. - 1570-9639 .- 1878-1454. ; 1749:1, s. 123-131
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Tidskriftsartikel (refereegranskat)abstract
- Lipoxygenases contain prosthetic iron, in human 5-lipoxygenase (5LO) the C-terminal isoleucine carboxylate constitutes one of five identified ligands. ATP is one of several factors determining 5LO activity. We compared properties of a series of 5LO C-terminal deletion mutants (one to six amino acid residues deleted). All mutants were enzymatically inactive (expected due to loss of iron), but expression yield (in E. coli) and affinity to ATP-agarose was markedly different. Deletion of up to four C-terminal residues was compatible with good expression and retained affinity to the ATP-column, as for wild-type 5LO. However when also the fifth residue was deleted (Asn-669) expression yield decreased and the affinity to ATP was markedly diminished. This was interpreted as a result of deranged structure and stability, due to loss of a hydrogen bond between Asn-669 and His-399. Mutagenesis of these residues supported this conclusion. In the structure of soybean lipoxygenase-1, a C-terminal loop was pointed out as important for correct orientation of the C-terminus. Accordingly, a hydrogen bond appears to stabilize such a C-terminal loop also in 5LO. © 2005 Elsevier B.V. All rights reserved.
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| 16. |
- Persson, Bengt, 1961-
(författare)
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Bioinformatics in Membrane Protein Analysis
- 2006
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Ingår i: Structural Genomics on Membrane Proteins. - Boca Raton : Taylor&Francis Group. ; , s. -400
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- While the genomic revolution has quickly led to the deposit of more than 30,000 structures in the protein data bank (PDB), less than one percent of those contributions represent membrane proteins despite the fact that membrane proteins constitute some 20 percent of all proteins. This discrepancy becomes significantly troublesome when it is coupled with the fact that 60 percent of current drugs are based on targeting this group of proteins, a trend that does not seem likely to reverse.Structural Genomics on Membrane Proteinsprovides an excellent overview on novel research in bioinformatics and modeling on membranes, as well as the latest technological developments being employed in expression, purification, and crystallography to obtain high-resolution structures on membrane proteins. This cutting-edge work also explains the difficulties facing researchers—both technical and ethical—that have slowed the process. Structural Genomics on Membrane Proteins provides researchers with an unprecedented look at the novel technologies that will ultimately allow them to conquer the last frontier in structural biology, leading to accelerated breakthroughs in drug discovery.
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| 17. |
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| 18. |
- Wahlström, Jan, et al.
(författare)
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Identification of HLA-DR-bound peptides presented by human bronchoalveolar lavage cells in sarcoidosis
- 2007
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Ingår i: Journal of Clinical Investigation. - 0021-9738 .- 1558-8238. ; 117:11, s. 3576-3582
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Tidskriftsartikel (refereegranskat)abstract
- Sarcoidosis is an inflammatory disease of unknown etiology, most commonly affecting the lungs. Activated CD4(+) T cells accumulate in the lungs of individuals with sarcoidosis and are considered to be of central importance for inflammation. We have previously shown that Scandinavian sarcoidosis patients expressing the HLADR allele DRB1*0301 are characterized by large accumulations in the lungs of CD4(+) T cells expressing the TCR AV2S3 gene segment. This association afforded us a unique opportunity to identify a sarcoidosis-specific antigen recognized by AV2S3(+) T cells. To identify candidates for the postulated sarcoidosis-specific antigen, lung cells from 16 HLA-DRB1*0301(pos) patients were obtained by bronchoalveolar lavage. HLA-DR molecules were affinity purified and bound peptides acid eluted. Subsequently, peptides were separated by reversed-phase HPLC and analyzed by liquid chromatography-mass spectrometry. We identified 78 amino acid sequences from self proteins presented in the lungs of sarcoidosis patients, some of which were well-known autoantigens such as vimentin and ATP synthase. For the first time, to our knowledge, we have identified HLA-bound peptides presented in vivo during an inflammatory condition. This approach can be extended to characterize HLA-bound peptides in various autoimmune settings.
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