| 11. |
- Kessler, Jan H., et al.
(author)
-
Antigen processing by nardilysin and thimet oligopeptidase generates cytotoxic T cell epitopes
- 2010
-
In: Nature Immunology. - : Springer Science and Business Media LLC. - 1529-2908 .- 1529-2916. ; 12:1, s. 45-53
-
Journal article (peer-reviewed)abstract
- Cytotoxic T lymphocytes (CTLs) recognize peptides presented by HLA class I molecules on the cell surface. The C terminus of these CTL epitopes is considered to be produced by the proteasome. Here we demonstrate that the cytosolic endopeptidases nardilysin and thimet oligopeptidase (TOP) complemented proteasome activity. Nardilysin and TOP were required, either together or alone, for the generation of a tumor-specific CTL epitope from PRAME, an immunodominant CTL epitope from Epstein-Barr virus protein EBNA3C, and a clinically important epitope from the melanoma protein MART-1. TOP functioned as C-terminal trimming peptidase in antigen processing, and nardilysin contributed to both the C-terminal and N-terminal generation of CTL epitopes. By broadening the antigenic peptide repertoire, nardilysin and TOP strengthen the immune defense against intracellular pathogens and cancer.
|
|
| 12. |
- Koeck, Thomas, et al.
(author)
-
A common variant in TFB1M is associated with reduced insulin secretion and increased future risk of type 2 diabetes.
- 2011
-
In: Cell Metabolism. - : Elsevier BV. - 1550-4131 .- 1932-7420. ; 13:1, s. 80-91
-
Journal article (peer-reviewed)abstract
- Type 2 diabetes (T2D) evolves when insulin secretion fails. Insulin release from the pancreatic β cell is controlled by mitochondrial metabolism, which translates fluctuations in blood glucose into metabolic coupling signals. We identified a common variant (rs950994) in the human transcription factor B1 mitochondrial (TFB1M) gene associated with reduced insulin secretion, elevated postprandial glucose levels, and future risk of T2D. Because islet TFB1M mRNA levels were lower in carriers of the risk allele and correlated with insulin secretion, we examined mice heterozygous for Tfb1m deficiency. These mice displayed lower expression of TFB1M in islets and impaired mitochondrial function and released less insulin in response to glucose in vivo and in vitro. Reducing TFB1M mRNA and protein in clonal β cells by RNA interference impaired complexes of the mitochondrial oxidative phosphorylation system. Consequently, nutrient-stimulated ATP generation was reduced, leading to perturbed insulin secretion. We conclude that a deficiency in TFB1M and impaired mitochondrial function contribute to the pathogenesis of T2D.
|
|
| 13. |
- Moles, A. T., et al.
(author)
-
Putting plant resistance traits on the map : A test of the idea that plants are better defended at lower latitudes
- 2011
-
In: New Phytologist. - : Wiley. - 0028-646X .- 1469-8137. ; 191:3, s. 777-788
-
Journal article (peer-reviewed)abstract
- It has long been believed that plant species from the tropics have higher levels of traits associated with resistance to herbivores than do species from higher latitudes. A meta-analysis recently showed that the published literature does not support this theory. However, the idea has never been tested using data gathered with consistent methods from a wide range of latitudes. • We quantified the relationship between latitude and a broad range of chemical and physical traits across 301 species from 75 sites world-wide. • Six putative resistance traits, including tannins, the concentration of lipids (an indicator of oils, waxes and resins), and leaf toughness were greater in high-latitude species. Six traits, including cyanide production and the presence of spines, were unrelated to latitude. Only ash content (an indicator of inorganic substances such as calcium oxalates and phytoliths) and the properties of species with delayed greening were higher in the tropics. • Our results do not support the hypothesis that tropical plants have higher levels of resistance traits than do plants from higher latitudes. If anything, plants have higher resistance toward the poles. The greater resistance traits of high-latitude species might be explained by the greater cost of losing a given amount of leaf tissue in low-productivity environments. © 2011 New Phytologist Trust.
|
|
| 14. |
|
|
| 15. |
- Rönnegård, Lars, et al.
(author)
-
Variance component and breeding value estimation for genetic heterogeneity of residual variance in Swedish Holstein dairy cattle
- 2013
-
In: Journal of Dairy Science. - : Elsevier. - 0022-0302 .- 1525-3198. ; 96:4, s. 2627-2636
-
Journal article (peer-reviewed)abstract
- Trait uniformity, or micro-environmental sensitivity, may be studied through individual differences in residual variance. These differences appear to be heritable, and the need exists, therefore, to fit models to predict breeding values explaining differences in residual variance. The aim of this paper is to estimate breeding values for micro-environmental sensitivity (vEBV) in milk yield and somatic cell score, and their associated variance components, on a large dairy cattle data set having more than 1.6 million records. Estimation of variance components, ordinary breeding values, and vEBV was performed using standard variance component estimation software (ASReml), applying the methodology for double hierarchical generalized linear models. Estimation using ASReml took less than 7 d on a Linux server. The genetic standard deviations for residual variance were 0.21 and 0.22 for somatic cell score and milk yield, respectively, which indicate moderate genetic variance for residual variance and imply that a standard deviation change in vEBV for one of these traits would alter the residual variance by 20%. This study shows that estimation of variance components, estimated breeding values and vEBV, is feasible for large dairy cattle data sets using standard variance component estimation software. The possibility to select for uniformity in Holstein dairy cattle based on these estimates is discussed.
|
|
| 16. |
|
|
| 17. |
- Stamenkovic, Jelena, et al.
(author)
-
Regulation of core clock genes in human islets.
- 2012
-
In: Metabolism, Clinical and Experimental. - : Elsevier BV. - 1532-8600. ; 61:7, s. 978-985
-
Journal article (peer-reviewed)abstract
- Nearly all mammalian cells express a set of genes known as clock genes. These regulate the circadian rhythm of cellular processes by means of negative and positive autoregulatory feedback loops of transcription and translation. Recent genomewide association studies have demonstrated an association between a polymorphism near the circadian clock gene CRY2 and elevated fasting glucose. To determine whether clock genes could play a pathogenetic role in the disease, we examined messenger RNA (mRNA) expression of core clock genes in human islets from donors with or without type 2 diabetes mellitus. Microarray and quantitative real-time polymerase chain reaction analyses were used to assess expression of the core clock genes CLOCK, BMAL-1, PER1 to 3, and CRY1 and 2 in human islets. Insulin secretion and insulin content in human islets were measured by radioimmunoassay. The mRNA levels of PER2, PER3, and CRY2 were significantly lower in islets from donors with type 2 diabetes mellitus. To investigate the functional relevance of these clock genes, we correlated their expression to insulin content and glycated hemoglobin levels: mRNA levels of PER2 (ρ = 0.33, P = .012), PER3 (ρ = 0.30, P = .023), and CRY2 (ρ = 0.37, P = .0047) correlated positively with insulin content. Of these genes, expression of PER3 and CRY2 correlated negatively with glycated hemoglobin levels (ρ = -0.44, P = .0012; ρ = -0.28, P = .042). Furthermore, in an in vitro model mimicking pathogenetic conditions, the PER3 mRNA level was reduced in human islets exposed to 16.7 mmol/L glucose per 1 mmol/L palmitate for 48 hours (P = .003). Core clock genes are regulated in human islets. The data suggest that perturbations of circadian clock components may contribute to islet pathophysiology in human type 2 diabetes mellitus.
|
|
| 18. |
- Strandberg, Erling, et al.
(author)
-
Statistical tools to select for robustness and milk quality
- 2013
-
In: Advances in Animal Biosciences. - : Cambridge University Press. - 2040-4700 .- 2040-4719. ; 4:3, s. 606-611
-
Journal article (peer-reviewed)abstract
- This work was part of the EU RobustMilk project. In this work package, we have focused on two aspects of robustness, micro- and macro-environmental sensitivity and applied these to somatic cell count (SCC), one aspect of milk quality. We showed that it is possible to combine both categorical and continuous descriptions of the environment in one analysis of genotype by environment interaction. We also developed a method to estimate genetic variation in residual variance and applied it to both simulated and a large field data set of dairy cattle. We showed that it is possible to estimate genetic variation in both micro- and macro-environmental sensitivity in the same data, but that there is a need for good data structure. In a dairy cattle example, this would mean at least 100 bulls with at least 100 daughters each. We also developed methods for improved genetic evaluation of SCC. We estimated genetic variance for some alternative SCC traits, both in an experimental herd data and in field data. Most of them were highly correlated with subclinical mastitis (>0.9) and clinical mastitis (0.7 to 0.8), and were also highly correlated with each other. We studied whether the fact that animals in different herds are differentially exposed to mastitis pathogens could be a reason for the low heritabilities for mastitis, but did not find strong evidence for that. We also created a new model to estimate breeding values not only for the probability of getting mastitis but also for recovering from it. In a progeny-testing situation, this approach resulted in accuracies of 0.75 and 0.4 for these two traits, respectively, which means that it is possible to also select for cows that recover more quickly if they get mastitis.
|
|
| 19. |
- Sun, Weilun, et al.
(author)
-
Improving the Cell Distribution in Collagen-Coated Poly-Caprolactone Knittings
- 2012
-
In: TISSUE ENG PART C-ME. - : Mary Ann Liebert Inc. - 1937-3384. ; 18:10, s. 731-739
-
Journal article (peer-reviewed)abstract
- Adequate cellular in-growth into biomaterials is one of the fundamental requirements of scaffolds used in regenerative medicine. Type I collagen is the most commonly used material for soft tissue engineering, because it is nonimmunogenic and a highly porous network for cellular support can be produced. However, in general, adequate cell in-growth and cell seeding has been suboptimal. In this study we prepared collagen scaffolds of different collagen densities and investigated the cellular distribution. We also prepared a hybrid polymer-collagen scaffold to achieve an optimal cellular distribution as well as sufficient mechanical strength. Collagen scaffolds [ranging from 0.3% to 0.8% (w/v)] with and without a mechanically stable polymer knitting [polycaprolactone (PCL)] were prepared. The porous structure of collagen scaffolds was characterized using scanning electron microscopy and hematoxylin-eosin staining. The mechanical strength of hybrid scaffolds (collagen with or without PCL) was determined using tensile strength analysis. Cellular in-growth and interconnectivity were evaluated using fluorescent bead distribution and human bladder smooth muscle cells and human urothelium seeding. The lower density collagen scaffolds showed remarkably deeper cellular penetration and by combining it with PCL knitting the tensile strength was enhanced. This study indicated that a hybrid scaffold prepared from 0.4% collagen strengthened with knitting achieved the best cellular distribution.
|
|
