| 1. |
- Åberg, Maria A I, 1972, et al.
(author)
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IGF-I has a direct proliferative effect in adult hippocampal progenitor cells.
- 2003
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In: Molecular and cellular neurosciences. - 1044-7431. ; 24:1, s. 23-40
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Journal article (peer-reviewed)abstract
- The aim of the present study was to investigate the potential direct effects of insulin-like growth factor-I (IGF-I) on adult rat hippocampal stem/progenitor cells (AHPs). IGF-I-treated cultures showed a dose-dependent increase in thymidine incorporation, total number of cells, and number of cells entering the mitosis phase. Pretreatment with fibroblast growth factor-2 (FGF-2) increased the IGF-I receptor (IGF-IR) expression, and both FGF-2 and IGF-I were required for maximal proliferation. Time-lapse recordings showed that IGF-I at 100 ng/ml decreased differentiation and increased proliferation of single AHPs. Specific inhibition of mitogen-activated protein kinase kinase (MAPKK), phosphatidylinositol 3-kinase (PI3-K), or the downstream effector of the PI3-K pathway, serine/threonine p70 S6 kinase (p70(S6K)), showed that both the MAPK and the PI3-K pathways participate in IGF-I-induced proliferation but that the MAPK activation is obligatory. These results were confirmed with dominant-negative constructs for these pathways. Stimulation of differentiation was found at a low dose (1 ng/ml) of IGF-I, clonal analysis indicating an instructive component of IGF-I signaling.
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| 2. |
- Åberg, N David, 1970, et al.
(author)
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Insulin-like growth factor-I increases astrocyte intercellular gap junctional communication and connexin43 expression in vitro.
- 2003
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In: Journal of neuroscience research. - : Wiley. - 0360-4012. ; 74:1, s. 12-22
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Journal article (peer-reviewed)abstract
- Connexin43 (cx43) forms gap junctions in astrocytes, and these gap junctions mediate intercellular communication by providing transport of low-molecular-weight metabolites and ions. We have recently shown that systemic growth hormone increases cx43 in the brain. One possibility was that local brain insulin-like growth factor-I (IGF-I) could mediate the effect by acting directly on astrocytes. In the present study, we examined the effects of direct application of recombinant human IGF-I (rhIGF-I) on astrocytes in primary culture concerning cx43 protein expression and gap junctional communication (GJC). After 24 hr of stimulation with rhIGF-I under serum-free conditions, the GJC and cx43 protein were analyzed. Administration of 30 ng/ml rhIGF-I increased the GJC and the abundance of cx43 protein. Cell proliferation of the astrocytes was not significantly increased by rhIGF-I at this concentration. However, a higher concentration of rhIGF-I (150 ng/ml) had no effect on GJC/cx43 but increased cell proliferation. Because of the important modulatory role of IGF binding proteins (IGFBPs) on IGF-I action, we analyzed IGFBPs in conditioned media. In cultures with a low abundance of IGFBPs (especially IGFBP-2), the GJC response to 30 ng/ml rhIGF-I was 81%, compared with the average of 25%. Finally, as a control, insulin was given in equimolar concentrations. However, GJC was not affected, which suggests that rhIGF-I acted via IGF-I receptors. In summary, the data show that rhIGF-I may increase GJC/cx43, whereas a higher concentration of rhIGF-I--at which stimulation of proliferation occurred--did not affect GJC/cx43. Furthermore, IGFBP-2 appeared to modulate the action of rhIGF-I on GJC in astrocytes by a paracrine mechanism.
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| 3. |
- Hellesen, Carl, 1980-, et al.
(author)
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Nuclear Spent Fuel Parameter Determination using Multivariate Analysis of Fission Product Gamma Spectra
- 2017
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In: Annals of Nuclear Energy. - : Elsevier BV. - 0306-4549 .- 1873-2100. ; 110, s. 886-895
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Journal article (peer-reviewed)abstract
- In this paper, we investigate the application of multivariate data analysis methods to the analysis of gamma spectroscopy measurements of spent nuclear fuel (SNF). Using a simulated irradiation and cooling of nuclear fuel over a wide range of cooling times (CT), total burnup at discharge (BU) and initial enrichments (IE) we investigate the possibilities of using a multivariate data analysis of the gamma ray emission signatures from the fuel to determine these fuel parameters. This is accomplished by training a multivariate analysis method on simulated data and then applying the method to simulated, but perturbed, data.We find that for SNF with CT less than about 20 years, a single gamma spectrum from a high resolution gamma spectrometer, such as a high-purity germanium spectrometer, allows for the determination of the above mentioned fuel parameters.Further, using measured gamma spectra from real SNF from Swedish pressurized light water reactors we were able to confirm the operator declared fuel parameters. In this case, a multivariate analysis trained on simulated data and applied to real data was used.
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| 4. |
- Johansson, Inger, 1962, et al.
(author)
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Proliferative and protective effects of growth hormone secretagogues on adult rat hippocampal progenitor cells.
- 2008
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In: Endocrinology. - : The Endocrine Society. - 0013-7227 .- 1945-7170. ; 149:5, s. 2191-9
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Journal article (peer-reviewed)abstract
- Progenitor cells in the subgranular zone of the hippocampus may be of significance for functional recovery after various injuries because they have a regenerative potential to form new neuronal cells. The hippocampus has been shown to express the GH secretagogue (GHS) receptor 1a, and recent studies suggest GHS to both promote neurogenesis and have neuroprotective effects. The aim of the present study was to investigate whether GHS could stimulate cellular proliferation and exert cell protective effects in adult rat hippocampal progenitor (AHP) cells. Both hexarelin and ghrelin stimulated increased incorporation of (3)H-thymidine, indicating an increased cell proliferation. Furthermore, hexarelin, but not ghrelin, showed protection against growth factor deprivation-induced apoptosis, as measured by annexin V binding and caspase-3 activity and also against necrosis, as measured by lactate dehydrogenase release. Hexarelin activated the MAPK and the phosphatidylinositol 3-kinase/Akt pathways, whereas ghrelin activated only the MAPK pathway. AHP cells did not express the GHS receptor 1a, but binding studies could show specific binding of both hexarelin and ghrelin, suggesting effects to be mediated by an alternative GHS receptor subtype. In conclusion, our results suggest a differential effect of hexarelin and ghrelin in AHP cells. We have demonstrated stimulation of (3)H-thymidine incorporation with both hexarelin and ghrelin. Hexarelin, but not ghrelin, also showed a significant inhibition of apoptosis and necrosis. These results suggest a novel cell protective and proliferative role for GHS in the central nervous system.
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| 5. |
- Lindgren, Martin, et al.
(author)
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Cognitive performance in late adolescence and long-term risk of early heart failure in Swedish men.
- 2018
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In: European journal of heart failure. - : Wiley. - 1879-0844 .- 1388-9842. ; 20:6, s. 989-97
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Journal article (peer-reviewed)abstract
- Heart failure (HF) incidence appears to increase among younger individuals, raising questions of how risk factors affect the younger population. We investigated the association of cognitive performance in late adolescence with long-term risk of early HF.We followed a cohort of Swedish men enrolled in mandatory military conscription in 1968-2005 (n=1 225 300; mean age 18.3years) until 2014 for HF hospitalization, using data from the Swedish National Inpatient Registry. Cognitive performance (IQ) was measured through a combination of tests, separately evaluating logical, verbal, visuospatial, and technical abilities. The results were standardized, weighted, and presented as stanines of IQ. The association between IQ and risk of HF was estimated using Cox proportional hazards models. In follow-up, there were 7633 cases of a first HF hospitalization (mean age at diagnosis 50.1years). We found an inverse relationship between global IQ and risk of HF hospitalization. Using the highest IQ stanine as reference, the adjusted hazard ratio for the lowest IQ with risk of HF was 3.11 (95% confidence interval 2.60-3.71), corresponding to a hazard ratio of 1.32 (95% CI 1.28-1.35) per standard deviation decrease of IQ. This association proved persistent across predefined categories of HF with respect to pre-existing or concomitant co-morbidities; it was less apparent among obese conscripts (P for interaction =0.0004).In this study of young men, IQ was strongly associated with increased risk of early HF. The medical profession needs to be aware of this finding so as to not defer diagnosis.
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| 6. |
- Senis, Lorenzo, et al.
(author)
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A computational methodology for estimating the detected energy spectra of the gamma-ray flux from irradiated nuclear fuel
- 2022
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In: IEEE Transactions on Nuclear Science. - : Institute of Electrical and Electronics Engineers (IEEE). - 0018-9499 .- 1558-1578. ; 69:4, s. 703-713
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Journal article (peer-reviewed)abstract
- Gamma-ray spectrometry using collimated detectors is a well-established examination method for irradiated nuclear fuel. However, the feasibility of examining a particular nuclide of interest is subject to constraints; the peak must be statistically determinable with the desired precision and the total spectrum count rate in the detector should not cause throughput issues. Methods were assembled for gamma spectrum prediction to optimize instruments for gamma emission tomography and to enable a priori feasibility evaluation of determination of single peaks of irradiated nuclear fuel. The aim was to find reliable results (~10% accuracy) regarding total spectrum and peak count rates with faster computation time than a full-Monte Carlo approach. For this purpose, the method is based on depletion calculations with SERPENT2, a point-source kernel method for the collimator response, a rig response matrix and a detector response matrix, both computed with MCNP6. The computational methodology uses as input the fuel properties (dimensions, materials, power history, and cooling time), and the instrumental setup (collimator and detector dimensions and materials). The prediction method was validated using measured data from a high-burnup, short-cooled test fuel rodlet from the Halden reactor. Absolute count rates and ratios of characteristic peaks were compared between predicted and measured spectra, showing a total count rate overestimation of 7% and discrepancies between 2-20% for the single peaks (same order of magnitude of the uncertainty). This level of agreement is deemed sufficient for measurement campaigns planning, and the optimization of spectroscopic instruments for use in gamma scanning and tomography of nuclear fuel.
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| 7. |
- Åberg, Maria A I, 1972, et al.
(author)
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Peripheral infusion of IGF-I selectively induces neurogenesis in the adult rat hippocampus.
- 2000
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In: The Journal of neuroscience : the official journal of the Society for Neuroscience. - 1529-2401. ; 20:8, s. 2896-903
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Journal article (peer-reviewed)abstract
- In several species, including humans, the dentate granule cell layer (GCL) of the hippocampus exhibits neurogenesis throughout adult life. The ability to regulate adult neurogenesis pharmacologically may be of therapeutic value as a mechanism for replacing lost neurons. Insulin-like growth factor-I (IGF-I) is a growth-promoting peptide hormone that has been shown to have neurotrophic properties. The relationship between IGF-I and adult hippocampal neurogenesis is to date unknown. The aim of this study was to investigate the effect of the peripheral administration of IGF-I on cellular proliferation in the dentate subgranular proliferative zone, which contains neuronal progenitor cells, and on the subsequent migration and differentiation of progenitor cells within the GCL. Using bromodeoxyuridine (BrdU) labeling, we found a significant increase of BrdU-immunoreactive progenitors in the GCL after 6 d of peripheral IGF-I administration. To determine the cell fate in progenitor progeny, we characterized the colocalization of BrdU-immunolabeled cells with cell-specific markers. In animals treated with IGF-I for 20 d, BrdU-positive cells increased significantly. Furthermore, the fraction of newly generated neurons in the GCL increased, as evaluated by the neuronal markers Calbindin D(28K), microtubule-associated protein-2, and NeuN. There was no difference in the fraction of newly generated astrocytes. Thus, our results show that peripheral infusion of IGF-I increases progenitor cell proliferation and selectively induces neurogenesis in the progeny of adult neural progenitor cells. This corresponds to a 78 +/- 17% (p < 0.001) increase in the number of new neurons in IGF-I-treated animals compared with controls.
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| 8. |
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| 9. |
- Åberg, N David, 1970, et al.
(author)
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Influence of Cardiovascular Fitness and Muscle Strength in Early Adulthood on Long-Term Risk of Stroke in Swedish Men
- 2015
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In: Stroke. - : Ovid Technologies (Wolters Kluwer Health). - 0039-2499 .- 1524-4628. ; 46:7, s. 1769-1776
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Journal article (peer-reviewed)abstract
- Background and Purpose Low cardiovascular fitness (fitness) in mid- and late life is a risk factor for stroke. However, the respective effects on long-term stroke risk of fitness and muscle strength in early adulthood are unknown. Therefore, we analyzed these in a large cohort of young men. Method We performed a population-based longitudinal cohort study of Swedish male conscripts registered in 1968 to 2005. Data on fitness (by the cycle ergometric test; n=1 166 035) and muscle strength (n=1 563 750) were trichotomized (low, medium, and high). During a 42-year follow-up, risk of stroke (subarachnoidal hemorrhage, intracerebral hemorrhage, and ischemic stroke) and fatality were calculated with Cox proportional hazards models. To identify cases, we used the International Classification of Diseases-Eighth to Tenth Revision in the Hospital Discharge Register and the Cause of Death Register. Results First-time stroke events were identified (subarachnoidal hemorrhage, n=895; intracerebral hemorrhage, n=2904; ischemic stroke, n=7767). For all stroke and fatality analysis any type of first-time stroke was recorded (n=10 917). There were inverse relationships in a dose-response fashion between fitness and muscle strength with any stroke (adjusted hazard ratios for the lowest, compared with the highest, tertile of each 1.70 [1.50-1.93] and 1.39 [1.27-1.53], respectively). There were stronger associations for fatal stroke. All 3 stroke types displayed similar associations. Associations between fitness and stroke remained when adjusted for muscle strength, whereas associations between muscle strength and stroke weakened/disappeared when adjusted for fitness. Conclusions At the age of 18 years, low fitness and to a lesser degree low muscle strength were independently associated with an increased future stroke risk.
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| 10. |
- Åberg, N David, 1970, et al.
(author)
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Peripheral infusion of insulin-like growth factor-I increases the number of newborn oligodendrocytes in the cerebral cortex of adult hypophysectomized rats.
- 2007
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In: Endocrinology. - : The Endocrine Society. - 0013-7227 .- 1945-7170. ; 148:8, s. 3765-72
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Journal article (peer-reviewed)abstract
- We have previously shown that recombinant human (rh) IGF-I induces cell proliferation and neurogenesis in the hippocampus of hypophysectomized rats. In the current investigation, we determined the effects of rhIGF-I on proliferation and differentiation in the cerebral cortex. Adult hypophysectomized rats were injected with bromodeoxyuridine (BrdU) to label newborn cells (once a day for the first 5 d), and rhIGF-I was administered peripherally for 6 or 20 d. In the cerebral cortex, the number of BrdU-labeled cells increased after 20 d but not after 6 d of rhIGF-I infusion. This suggests that rhIGF-I enhances the survival of newborn cells in the cerebral cortex. Using BrdU labeling combined with the oligodendrocyte-specific markers myelin basic protein and 2',3'-cyclic nucleotide 3'-phosphodiesterase, we demonstrated an increase in oligodendrogenesis in the cerebral cortex. The total amount of myelin basic protein and 2',3'-cyclic nucleotide 3'-phosphodiesterase was also increased on Western blots of homogenates of the cerebral cortex, confirming the immunohistochemical findings. Also, we observed an increase in the number of capillary-associated BrdU-positive cells, although total capillary area was not increased. rhIGF-I treatment did not affect cortical astrogliogenesis and neurogenesis was not observed. The ability of rhIGF-I to induce cortical oligodendrogenesis may have implications for the regenerative potential of the cortex.
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