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| 2. |
- Liu, Kui, et al.
(författare)
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Kallikrein genes are associated with lupus and glomerular basement membrane-specific antibody-induced nephritis in mice and humans
- 2009
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Ingår i: Journal of Clinical Investigation. - 0021-9738 .- 1558-8238. ; 119:4, s. 911-923
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Tidskriftsartikel (refereegranskat)abstract
- Immune-mediated nephritis contributes to disease in systemic lupus erythematosus, Goodpasture syndrome (caused by antibodies specific for glomerular basement membrane [anti-GBM antibodies]), and spontaneous lupus nephritis. Inbred mouse strains differ in susceptibility to anti-GBM antibody-induced and spontaneous lupus nephritis. This study sought to clarify the genetic and molecular factors that maybe responsible for enhanced immune-mediated renal disease in these models. When the kidneys of 3 mouse strains sensitive to anti-GBM antibody-induced nephritis were compared with those of 2 control strains using microarray analysis, one-fifth of the underexpressed genes belonged to the kallikrein gene family,which encodes serine esterases. Mouse strains that upregulated renal and urinary kallikreins exhibited less evidence of disease. Antagonizing the kallikrein pathway augmented disease, while agonists dampened the severity of anti-GBM antibody-induced nephritis. In addition, nephritis-sensitive mouse strains had kallikrein haplotypes that were distinct from those of control strains, including several regulatory polymorphisms,some of which were associated with functional consequences. Indeed, increased susceptibility to anti-GBM antibody-induced nephritis and spontaneous lupus nephritis was achieved by breeding mice with a genetic interval harboring the kallikrein genes onto a disease-resistant background. Finally, both human SLE and spontaneous lupus nephritis were found to be associated with kallikrein genes, particularly KLK1 and the KLK3 promoter, when DNA SNPs from independent cohorts of SLE patients and controls were compared. Collectively, these studies suggest that kallikreins are protective disease-associated genes in anti-GBM antibody-induced nephritis and lupus.
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| 3. |
- Borén, Jan, 1963, et al.
(författare)
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In situ localization of transketolase activity in epithelial cells of different rat tissues and subcellularly in liver parenchymal cells
- 2006
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Ingår i: J Histochem Cytochem. - 0022-1554. ; 54:2, s. 191-9
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Tidskriftsartikel (refereegranskat)abstract
- Metabolic mapping of enzyme activities (enzyme histochemistry) is an important tool to understand (patho)physiological functions of enzymes. A new enzyme histochemical method has been developed to detect transketolase activity in situ in various rat tissues and its ultrastructural localization in individual cells. In situ detection of transketolase is important because this multifunctional enzyme has been related with diseases such as cancer, diabetes, Alzheimer's disease, and Wernicke-Korsakoff's syndrome. The proposed method is based on the tetrazolium salt method applied to unfixed cryostat sections in the presence of polyvinyl alcohol. The method appeared to be specific for transketolase activity when the proper control reaction is performed and showed a linear increase of the amount of final reaction product with incubation time. Transketolase activity was studied in liver, small intestine, trachea, tongue, kidney, adrenal gland, and eye. Activity was found in liver parenchyma, epithelium of small intestine, trachea, tongue, proximal tubules of kidney and cornea, and ganglion cells in medulla of adrenal gland. To demonstrate transketolase activity ultrastructurally in liver parenchymal cells, the cupper iron method was used. It was shown that transketolase activity was present in peroxisomes and at membranes of granular endoplasmic reticulum. This ultrastructural localization is similar to that of glucose-6-phosphate dehydrogenase activity, suggesting activity of the pentose phosphate pathway at these sites. It is concluded that the method developed for in situ localization of transketolase activity for light and electron microscopy is specific and allows further investigation of the role of transketolase in (proliferation of) cancer cells and other pathophysiological processes.
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| 4. |
- Bunce, R. G. H., et al.
(författare)
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A standardized procedure for surveillance and monitoring European habitats and provision of spatial data
- 2008
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Ingår i: Landscape Ecology. - : Springer Science and Business Media LLC. - 0921-2973 .- 1572-9761. ; 23, s. 11-25
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Tidskriftsartikel (refereegranskat)abstract
- Both science and policy require a practical, transmissible, and reproducible procedure for surveillance and monitoring of European habitats, which can produce statistics integrated at the landscape level. Over the last 30 years, landscape ecology has developed rapidly, and many studies now require spatial data on habitats. Without rigorous rules, changes from baseline records cannot be separated reliably from background noise. A procedure is described that satisfies these requirements and can provide consistent data for Europe, to support a range of policy initiatives and scientific projects. The methodology is based on classical plant life forms, used in biogeography since the nineteenth century, and on their statistical correlation with the primary environmental gradient. Further categories can therefore be identified for other continents to assist large scale comparisons and modelling. The model has been validated statistically and the recording procedure tested in the field throughout Europe. A total of 130 General Habitat Categories (GHCs) is defined. These are enhanced by recording environmental, site and management qualifiers to enable flexible database interrogation. The same categories are applied to areal, linear and point features to assist recording and subsequent interpretation at the landscape level. The distribution and change of landscape ecological parameters, such as connectivity and fragmentation, can then be derived and their significance interpreted.
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| 5. |
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| 6. |
- Anton, R., et al.
(författare)
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Refrigerating Cycle Simulator : System Modelling, Educational Implementation and Assessment
- 2009
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Ingår i: International journal of engineering education. - 0949-149X. ; 25:2, s. 324-332
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Tidskriftsartikel (refereegranskat)abstract
- To leach and explain system modelling in a Thermal-Fluid application is a challenge: learning how one component or even the surrounding conditions can influence the performance of the rest of the components of the system and the system itself is not all easy task. However a suitable educational implementation may help students gain a deeper understanding not only of the system itself bill of the existing interrelation between the Thermal-Fluid fields: Thermodynamics, Heat Transfer and Fluid Mechanics. In this study a refrigerating cycle simulator is used. The simulator is' prepared in such a way that the interrelation between each component, the system and the surroundings call be analysed by the students. This case study is found to be very useful due of its ability to study system performance. A three-step educational implementation, the simulator being the third step, has been used and found to he enriching both for students and instructors.
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| 7. |
- Baroni, Mpma, et al.
(författare)
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Modeling and gradient pattern analysis of irregular SFM structures of porous silicon
- 2006
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Ingår i: Microelectronics Journal. - : Elsevier BV. - 0026-2692. ; 37:4, s. 290-294
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Tidskriftsartikel (refereegranskat)abstract
- Technological applications in opto-electronic devices have increased the interest in characterizing porous silicon structure patterns. Due to its physical properties, solutions from KPZ 2D are adopted to simulate the structure of porous material interface whose spatial characteristics are equivalent to those found in porous silicon samples. The analysis of the simulated and real scanning Force Microscopy (SFM) surfaces was done using the Gradient Pattern Analysis (GPA). We found that the KPZ 2D model presented asymmetry levels compatible with the irregular surfaces observed by means of SFM images of pi-Si.
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| 8. |
- Dourado, Daniel F A R, et al.
(författare)
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Glutathione transferase : new model for glutathione activation
- 2008
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Ingår i: Chemistry - A European Journal. - : Wiley. - 0947-6539 .- 1521-3765. ; 14:31, s. 9591-8
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Tidskriftsartikel (refereegranskat)abstract
- Glutathione transferases are enzymes of the cellular detoxification system that metabolize a vast spectrum of xenobiotic and endobiotic toxic compounds. They are homodimers or heterodimers and each monomer has an active center composed of a G-site in which glutathione (GSH) binds and an H-site for the electrophilic substrate. When GSH binds to the G-site, the pKa value of its thiol group drops by 2.5 units; this promotes its deprotonation and, therefore, produces a strong nucleophilic thiolate that is able to react with the electrophilic substrate. The mechanism behind the deprotonation of the thiol group is still unknown. Some studies point to the fact that the GSH glutamyl alpha-carboxylate group is essential for GSH activation, whereas others indicate the importance of the active-center water molecules. On the basis of QM/MM calculations, we propose a mechanism of GSH activation in which a water molecule, acting as a bridge, is able to assist in the transfer of the proton from the GSH thiol group to the GSH glutamyl alpha-carboxylate group, after an initial GSH conformational rearrangement. We calculated the potential of mean force of this GSH structural rearrangement that would be necessary for the approach of both groups and we then performed a QM/MM ONIOM scan of water-assisted proton transfer. The overall free-energy barrier for the process is consistent with experimental studies of the enzyme kinetics.
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| 9. |
- Dutt, Amit, et al.
(författare)
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Drug-sensitive FGFR2 mutations in endometrial carcinoma
- 2008
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 105:25, s. 8713-8717
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Tidskriftsartikel (refereegranskat)abstract
- Oncogenic activation of tyrosine kinases is a common mechanism of carcinogenesis and, given the druggable nature of these enzymes, an attractive target for anticancer therapy. Here, we show that somatic mutations of the fibroblast growth factor receptor 2 (FGFR2) tyrosine kinase gene, FGFR2, are present in 12% of endometrial carcinomas, with additional instances found in lung squamous cell carcinoma and cervical carcinoma. These FGFR2 mutations, many of which are identical to mutations associated with congenital craniofacial developmental disorders, are constitutively activated and oncogenic when ectopically expressed in NIH 3T3 cells. Inhibition of FGFR2 kinase activity in endometrial carcinoma cell lines bearing such FGFR2 mutations inhibits transformation and survival, implicating FGFR2 as a novel therapeutic target in endometrial carcinoma.
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