| 1. |
|
|
| 2. |
|
|
| 3. |
- Farrokhnia, Nasim, et al.
(author)
-
Differential early mitogen-activated protein kinase activation in hyperglycemic ischemic brain injury in the rat
- 2005
-
In: European Journal of Clinical Investigation. - : Wiley. - 0014-2972 .- 1365-2362. ; 35:7, s. 457-463
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Hyperglycemia aggravates brain injury induced by focal ischemia-reperfusion. The mitogen-activated protein kinase (MAPK) members extracellular-signal regulated kinase (Erk) and c-Jun N-terminal kinase (JNK) have been proposed as mediators of ischemic brain injury, and Erk is strongly activated by combined hyperglycemia and transient global ischemia. It is unclear whether similar MAPK activation appears in focal brain ischemia with concomitant hyperglycemia. DESIGN: Hyperglycemia was induced in rats by an intraperitoneal bolus of glucose (2 g kg(-1)). The rats were then subjected to 90 min of transient middle cerebral artery occlusion (MCAO). Erk and JNK activation were investigated with immunofluorescence and Western blot along with infarct size measurement based on tetrazolium staining and neurological score. RESULTS: The hyperglycemic rats showed increased tissue damage and impaired neurological performance after 1 day compared with controls. The hyperglycemia was generally moderate (< 15 mM). Erk activation was increased after 30 min of reperfusion in the ischemic cortex of the hyperglycemic rats, while JNK activation was present on the contralateral side. Phospho-Erk immunofluorescence revealed marked neuronal activation of Erk in the ischemic cortex of hyperglycemic rats compared with controls. CONCLUSION: Besides confirming the detrimental effects of hyperglycemia on focal ischemia-reperfusion, this study shows that hyperglycemia strongly activates the pathogenic mediator Erk in the ischemic brain in the early phase of reperfusion. JNK activation at this stage is present in the nonischemic hemisphere. The functional relevance of these findings needs further investigation.
|
|
| 4. |
|
|
| 5. |
- Farrokhnia, Nasim, et al.
(author)
-
Experimental treatment for focal hyperglycemic ischemic brain injury in the rat
- 2005
-
In: Experimental Brain Research. - : Springer Science and Business Media LLC. - 0014-4819 .- 1432-1106. ; 167:2, s. 310-314
-
Journal article (peer-reviewed)abstract
- Hyperglycemia aggravates ischemic brain injury, possibly due to the activation of signaling pathways involving reactive oxygen species, Src and mitogen-activated protein kinases. The aim of this study was to investigate the effects of the spin trap agent alpha-phenyl-N-tert-butyl nitrone (PBN), the Src family kinase inhibitor PP2 and the MEK1-inhibitor U0126 on focal hyperglycemic ischemic brain injury. Temporary middle cerebral artery occlusion (90 min) was induced in four groups of rats (PBN, PP2, and U0126 vs. control). Neurological testing and tetrazolium red staining were performed after 1 day. PBN decreased the infarct volume by 70% compared with the control (P<0.05) and a tendency towards reduced infarcts was seen in the PP2 or U0126 groups. Furthermore, neurological testing was consistent with the volumetric analysis. In conclusion, PBN appears to be a potential neuroprotective agent in hyperglycemic, focal ischemic brain injury, while the efficacy of PP2 and U0126 could not be confirmed by the present data.
|
|
| 6. |
- Jonasson, Mats, et al.
(author)
-
Design and evaluation of an active electromechanical wheel suspension system
- 2008
-
In: Mechatronics (Oxford). - : Elsevier BV. - 0957-4158 .- 1873-4006. ; 18:4, s. 218-230
-
Journal article (peer-reviewed)abstract
- This paper presents an electromechanical wheel suspension, where the upper arm of the suspension has been provided with an electric levelling and a damper actuator, both are allowed to work in a fully active mode. A control structure for the proposed suspension is described. The complex design task involving the control of the electric damper and its machine parameters is tackled by genetic optimisation. During this process, these parameters are optimised to keep the power dissipation of the electric damper as low as possible, while maintaining acceptable comfort and road-holding capabilities. The results of the evaluations carried out demonstrate that the proposed suspension can easily adopt its control parameters to obtain a better compromise of performance than that offered by passive suspensions. If the vehicle is to maintain acceptable performance during severe driving conditions, the damper has to be unrealistically large. However, if the electric damper is combined with a hydraulic damper, the size of the electric damper is significantly reduced. In addition, the design of the electric damper with the suggested control structure, including how it regenerates energy, is discussed.
|
|
| 7. |
- Kepka, Cecilia, et al.
(author)
-
Two-step recovery process for tryptophan tagged cutinase : Interfacing aqueous two-phase extraction and hydrophobic interaction chromatography
- 2005
-
In: Journal of Chromatography A. - : Elsevier BV. - 0021-9673 .- 1873-3778. ; 1075:02-jan, s. 33-41
-
Journal article (peer-reviewed)abstract
- In this work, the interfacing of a poly(ethylene glycol) (PEG)-phosphate aqueous two-phase system with hydrophobic interaction chromatography (HIC) for primary recovery of an intracellular protein was evaluated. As a model protein, a recombinant cutinase furnished with a tryptophan-proline (WP) peptide tag was used and produced intracellularly in Escherichia coli (E. coli). E. coli cell homogenate was partitioned in a two-phase system and the top phase yield, concentration and purity of the tagged ZZ-cutinase-(WP)(4) was evaluated as function of polymer sizes, system pH and phase volume ratio. The partition behaviour of cell debris, total protein and endotoxin was also monitored. In the HIC part, the chromatographic yield and purity was investigated with respect to ligand hydrophobicity, dilution of loaded top phase and elution conditions. Based on the results, a recovery process was demonstrated where a PEG 1500-K-Na phosphate salt aqueous two-phase system was interfaced with a HIC column. The interfacing was facilitated by the Trp-tagged peptide. The tagged ZZ-cutinase-(WP)4 was obtained in a PEG-free phase and purified to > 95% purity according to silver stained sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) gels with a total yield of 83% during the two-step recovery process. © 2005 Elsevier B.V. All rights reserved.
|
|
| 8. |
- Nordfjäll, Katarina, et al.
(author)
-
The individual blood cell telomere attrition rate is telomere length dependent.
- 2009
-
In: PLoS genetics. - : Public Library of Science. - 1553-7404. ; 5:2, s. e1000375-
-
Journal article (peer-reviewed)abstract
- Age-associated telomere shortening is a well documented feature of peripheral blood cells in human population studies, but it is not known to what extent these data can be transferred to the individual level. Telomere length (TL) in two blood samples taken at approximately 10 years interval from 959 individuals was investigated using real-time PCR. TL was also measured in 13 families from a multigenerational cohort. As expected, we found an age-related decline in TL over time (r = -0.164, P<0.001, n = 959). However, approximately one-third of the individuals exhibited a stable or increased TL over a decade. The individual telomere attrition rate was inversely correlated with initial TL at a highly significant level (r = -0.752, P<0.001), indicating that the attrition rate was most pronounced in individuals with long telomeres at baseline. In accordance, the age-associated telomere attrition rate was more prominent in families with members displaying longer telomeres at a young age (r = -0.691, P<0.001). Abnormal blood TL has been reported at diagnosis of various malignancies, but in the present study there was no association between individual telomere attrition rate or prediagnostic TL and later tumor development. The collected data strongly suggest a TL maintenance mechanism acting in vivo, providing protection of short telomeres as previously demonstrated in vitro. Our findings might challenge the hypothesis that individual TL can predict possible life span or later tumor development.
|
|
| 9. |
- Orho-Melander, Marju, et al.
(author)
-
Common Missense Variant in the Glucokinase Regulatory Protein Gene Is Associated With Increased Plasma Triglyceride and C-Reactive Protein but Lower Fasting Glucose Concentrations
- 2008
-
In: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 57:11, s. 3112-3121
-
Journal article (peer-reviewed)abstract
- OBJECTIVE-Using the genome-wide association approach, we recently identified the glucokinase regulatory protein gene (GCKR, rs780094) region as a novel quantitative trait locus for plasma triglyceride concentration in Europeans. Here, we sought to study the association of GCKR variants with metabolic phenotypes, including measures of glucose homeostasis, to evaluate the GCYR locus in samples of non-European ancestry and to fine-map across the associated genomic interval. RESEARCH DESIGN AND METHODS-We performed association studies in 12 independent cohorts comprising >45,000 individuals representing several ancestral groups (whites from Northern and Southern Europe, whites from the U.S., African Americans from the U.S., Hispanics of Caribbean origin, and Chinese, Malays, and Asian Indians from Singapore). We conducted genetic fine-mapping across the similar to 417-kb region of linkage disequilibrium. spanning GCKR and 16 other genes on chromosome 2p23 by imputing untyped HapMap single nucleotide polymorphisms (SNPs) and genotyping 104 SNPs across the associated genomic interval. RESULTS-We provide comprehensive evidence that GCYR rs780094 is associated with opposite effects on fasting plasma triglyceride (P-meta = 3 x 10(-56)) and glucose (P-meta = 1 x 10(-13)) concentrations. In addition, we confirmed recent reports that the same SNP is associated with C-reactive protein (CRP) level (P = 5 x 10(-5)). Both fine-mapping approaches revealed a common missense GCKR variant (rs1260326, Pro446Leu, 34% frequency, r(2) = 0.93 with rs780094) as the strongest association signal in the region. CONCLUSIONS-These findings point to a molecular mechanism in humans by which higher triglycerides and CRP can be coupled with lower plasma glucose concentrations and position GCKR in central pathways regulating both hepatic triglyceride and glucose metabolism. Diabetes 57:3112-3121, 2008
|
|
| 10. |
- Palmqvist, Richard, et al.
(author)
-
hTERT gene copy number is not associated with hTERT RNA expression or telomerase activity in colorectal cancer
- 2005
-
In: International Journal of Cancer. - Geneve : International union against cancer. - 0020-7136 .- 1097-0215. ; 116:3, s. 395-400
-
Journal article (peer-reviewed)abstract
- In a majority of malignant human tumors telomerase activity can be detected, suggesting an immortal phenotype. Expression of the reverse transcriptase subunit, hTERT, in the human telomerase complex is required for telomerase activity. The regulation of hTERT, from gene level to a fully functional protein, is still a poorly understood process. Increased copy number of the hTERT gene has been demonstrated in a significant portion of established cell lines and tumors of different origin but its relevance for telomerase activity levels is unclear. In the present study, we examined the hTERT gene copy number using fluorescence in situ hybridization (FISH) in samples from 64 colorectal carcinomas and an increased copy number (≥ 3 hTERT gene copies/nucleus) was observed in 31 cases (48%). No statistical association existed between hTERT gene copy number and hTERT RNA expression or telomerase activity. However, a significant relationship was found between an increase in hTERT gene copy number and p53 protein accumulation (p = 0.002) and aneuploidy (p = 0.036). Only 4 tumors showed microsatellite instability, 3 of which had a normal hTERT gene copy number. The data indicated that the increased copy number of the hTERT gene in colorectal carcinoma was a result of genomic instability with no obvious consequence for telomerase activity levels.
|
|
