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| 3. |
- Ling, Charlotte, et al.
(författare)
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Genetic and epigenetic factors are associated with expression of respiratory chain component NDUFB6 in human skeletal muscle.
- 2007
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Ingår i: The Journal of clinical investigation. - 0021-9738. ; 117:11, s. 3427-35
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Tidskriftsartikel (refereegranskat)abstract
- Insulin resistance and type 2 diabetes are associated with decreased expression of genes that regulate oxidative phosphorylation in skeletal muscle. To determine whether this defect might be inherited or acquired, we investigated the association of genetic, epigenetic, and nongenetic factors with expression of NDUFB6, a component of the respiratory chain that is decreased in muscle from diabetic patients. Expression of NDUFB6 was influenced by age, with lower gene expression in muscle of elderly subjects. Heritability of NDUFB6 expression in muscle was estimated to be approximately 60% in twins. A polymorphism in the NDUFB6 promoter region that creates a possible DNA methylation site (rs629566, A/G) was associated with a decline in muscle NDUFB6 expression with age. Although young subjects with the rs629566 G/G genotype exhibited higher muscle NDUFB6 expression, this genotype was associated with reduced expression in elderly subjects. This was subsequently explained by the finding of increased DNA methylation in the promoter of elderly, but not young, subjects carrying the rs629566 G/G genotype. Furthermore, the degree of DNA methylation correlated negatively with muscle NDUFB6 expression, which in turn was associated with insulin sensitivity. Our results demonstrate that genetic, epigenetic, and nongenetic factors associate with NDUFB6 expression in human muscle and suggest that genetic and epigenetic factors may interact to increase age-dependent susceptibility to insulin resistance.
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| 4. |
- Andersson, Bodil, et al.
(författare)
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Treatment and outcome in pancreatic pseudocysts
- 2006
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 41:6, s. 751-756
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Tidskriftsartikel (refereegranskat)abstract
- Objective. Pancreatic pseudocyst is a common complication of both acute and chronic pancreatitis. The aim of the present study was to evaluate the efficacy and complications of different treatment regimens. Material and methods. All patients >= 15 years of age admitted to Lund University Hospital from 1994 to 2003 with pancreatic pseudocysts were analysed retrospectively. Pseudocysts were defined according to the Atlanta classification. Results. Forty-four patients (29 M (66%), mean age 559/14 years) were included in the study, and all were subjected to treatment on totally 88 occasions. Mean size of pseudocysts at diagnosis was 9.69 +/- 6.8 cm (1.5-40 cm). Recurrence after treatment was 1.0 +/- 1.1 times (range 0-4). No difference was found in recurrence rate or pseudocyst size when comparing conservative versus interventional treatment, but patient weight was higher (p=0.013) and acute pancreatitis was more frequent (p=0.046) in conservatively treated patients. Surgical treatment tended to be associated with a lower recurrence rate as compared with percutaneous treatments. The rate of hospital admissions was in median 3 (0-16) and median length of stay (LOS) was 12 days (0-141 days). Six patients (14%) had complications and 3 died (7%). Pseudocysts >= 8 cm did not differ significantly from smaller pseudocysts regarding the choice of conservative treatment, LOS, recurrence and gastrointestinal obstruction, but there was a trend towards more complications in the group with larger pseudocysts ( 5 versus 1). Conclusions. Patients with pancreatic pseudocysts require frequent hospital admissions and repeated treatments. Larger pseudocysts do not imply more recurrences. The lowest recurrence rate overall was seen after open surgery.
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- Askerlund, Therese, et al.
(författare)
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Småbarnsföräldrars konsumentbeteende : En kvantitativ studie om engagemang, säkerhetstänkande, värderingar och omgivningens påverkan på köpbeslut
- 2008
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Den här boken är resultat av åtta studenters arbete under en uppsatsperiod på tio veckor. Vi började träffas i mars 2008 och i april satte arbetet igång på allvar. Under perioden gjorde studenterna en enkät, samlade in data och analyserade för att komma fram till hur småbarnsföräldrar funderar kring inköp av artiklar åt sina barn. I slutet av maj var arbetet klart! Det har varit ett nöje att få handleda arbetet och jag känner mig stolt att som handledare få presentera den här boken, vars innehåll är väldigt rikt med tanke på under vilken kort period den skapats. Jag hoppas att den kommer att läsas av studenter i marknadsföring som vill ha inspiration till hur undersökningar om konsumentbeteende kan genomföras, eller som helt enkelt bara vill läsa sig mer om ämnet. Vi vill alla tacka några personer som engagerat sig i att hjälpa till med arbetet, genom att låta sig intervjuas, släppa in oss i sällskap av konsumerande föräldrar eller givit synpunkter på arbetet som helhet. Tack till Linn Söderlund, Nicolaus Eberhardt och Maria Hedlund. Cecilia Lindh, Maj 2008
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| 6. |
- Berglund, Lisa, et al.
(författare)
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A genecentric Human Protein Atlas for expression profiles based on antibodies
- 2008
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Ingår i: Molecular & Cellular Proteomics. - 1535-9476 .- 1535-9484. ; 7:10, s. 2019-2027
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Forskningsöversikt (refereegranskat)abstract
- An attractive path forward in proteomics is to experimentally annotate the human protein complement of the genome in a genecentric manner. Using antibodies, it might be possible to design protein-specific probes for a representative protein from every protein-coding gene and to subsequently use the antibodies for systematical analysis of cellular distribution and subcellular localization of proteins in normal and disease tissues. A new version (4.0) of the Human Protein Atlas has been developed in a genecentric manner with the inclusion of all human genes and splice variants predicted from genome efforts together with a visualization of each protein with characteristics such as predicted membrane regions, signal peptide, and protein domains and new plots showing the uniqueness (sequence similarity) of every fraction of each protein toward all other human proteins. The new version is based on tissue profiles generated from 6120 antibodies with more than five million immunohistochemistry-based images covering 5067 human genes, corresponding to approximately 25% of the human genome. Version 4.0 includes a putative list of members in various protein classes, both functional classes, such as kinases, transcription factors, G-protein-coupled receptors, etc., and project-related classes, such as candidate genes for cancer or cardiovascular diseases. The exact antigen sequence for the internally generated antibodies has also been released together with a visualization of the application-specific validation performed for each antibody, including a protein array assay, Western blot analysis, immunohistochemistry, and, for a large fraction, immunofluorescence-based confocal microscopy. New search functionalities have been added to allow complex queries regarding protein expression profiles, protein classes, and chromosome location. The new version of the protein atlas thus is a resource for many areas of biomedical research, including protein science and biomarker discovery.
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| 7. |
- Carlén, Emma, et al.
(författare)
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Random regression models for genetic evaluation of clinical mastitis in dairy cattle
- 2009
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Ingår i: Animal. - 1751-7311 .- 1751-732X. ; 3, s. 1100-1108
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Tidskriftsartikel (refereegranskat)abstract
- A genetic analysis of longitudinal binary clinical mastitis (CM) data recorded on about 90000 first-lactation Swedish Holstein cows was carried out using linear random regression models (RRM). This method for genetic evaluation of CM has theoretical advantages compared to the method of linear cross-sectional models (CSM), which is currently being used The aim of this study was to investigate the feasibility and suitability of estimating genetic parameters and predicting breeding values for CM with a linear sire RRM. For validation purposes, the estimates and predictions from the RRM were compared to those from linear sire longitudinal multivariate models (LMVM) and CSM. For each cow, the period from 10 days before to 241 days after calving was divided into four 1-week intervals followed by eight 4-week intervals. Within each interval, presence or absence of CM was scored as '1' or '0' The linear RRM used to explain the trajectory of CM over time included a set of explanatory variables plus a third-order Legendre polynomial function of time for the sire effect The time-dependent heritabilities and genetic correlations from the chosen RRM corresponded fairly well with estimates obtained from the linear LMVM for the separate intervals. Some discrepancy between the two methods was observed, with the more unstable results being obtained from the linear LMVM. Both methods indicated clearly that CM was not genetically the same trait throughout lactation. The correlations between predicted sire breeding values from the RRM, summarized over different time periods, and from linear CSM were rather high. They were, however, less than unity (0.74 to 0.96), which indicated some re-ranking of sires. Sire curves based on the time-specific breeding values from the RRM illustrated differences in intercept and slope among the best and the worst sires. To conclude, a linear sire RRM seemed to work well for genetic evaluation purposes, but was sensitive for estimation of genetic parameters.
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| 8. |
- Cumpstey, Ian, et al.
(författare)
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Double Affinity Amplification of Galectin-Ligand Interactions through Arginine-Arene Interactions: Synthetic, Thermodynamic, and Computational Studies with Aromatic Diamido-Thiodigalactosides.
- 2008
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Ingår i: Chemistry: A European Journal. - : Wiley. - 1521-3765 .- 0947-6539. ; 14:14, s. 4233-4245
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Tidskriftsartikel (refereegranskat)abstract
- A series of aromatic mono- or diamido-thiodigalactoside derivatives were synthesized and studied as ligands for galectin-1, -3, -7, -8N terminal domain, and -9N terminal domain. The affinity determination in vitro with competitive fluorescence-polarization experiments and thermodynamic analysis by isothermal microcalorimetry provided a coherent picture of structural requirements for arginine-arene interactions in galectin-ligand binding. Computational studies were employed to explain binding preferences for the different galectins. Galectin-3 formed two almost ideal arene-arginine stacking interactions according to computer modeling and also had the highest affinity for the diamido-thiodigalactosides (K(d) below 50 nM). Site-directed mutagenesis of galectin-3 arginines involved in binding corroborated the importance of their interaction with the aromatic diamido-thiodigalactosides. Furthermore, the arginine mutants revealed distinct differences between free, flexible, and solvent-exposed arginine side chains and tightly ion-paired arginine side chains in interactions with aromatic systems.
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| 9. |
- Cumpstey, Ian, et al.
(författare)
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Studies of arginine-arene interactions through synthesis and evaluation of a series of galectin-binding aromatic lactose esters
- 2007
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Ingår i: ChemBioChem. - : Wiley. - 1439-4227 .- 1439-7633. ; 8:12, s. 1389-1398
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Tidskriftsartikel (refereegranskat)abstract
- Aromatic lactose 2-O-esters were synthesized and used to probe arene-arginine interactions with the galectin family of proteins. They were found to be low mu m inhibitors of galectin-1, -3, and -9N-terminal domain and moderate inhibitors of galectin-7, but not inhibitors of galectin-8N-terminal, which locks an arginine residue close to the critical, esterified lactose 2-O-position. Molecular modeling of galectins in complex with aromatic lactose 2-O-esters, as well as binding studies with a galectin-3 R186S mutant, confirmed that the inhibitory efficiency of the lactose 2-O-esters was due to the formation of strong interactions between the aromatic ester moieties and the arginine guanidinium groups of galectin-1 and -3. An important common feature shared by galectin-1 and -3 was that the arginines formed in-plane ion pairs with two side-chain carboxylates, which resulted in extended planar pi-electron surfaces that did not require solvation by water; these surfaces were ideal for stocking with aromatic moieties of the ligands. The results provide a basis for the design of lectin inhibitors and drugs that exploit interactions with arginine side-chains via aromatic moieties, which are involved in intramolecular protein salt bridges.
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