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- Lindqvist, Daniel, et al.
(författare)
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Circulating Cell-Free Mitochondrial DNA - a Novel Marker of Mitochondrial Stress Associated With Suicidality and Major Depressive Disorder
- 2018
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Ingår i: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 83:9, suppl. 1, s. S25-S26
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Mitochondrial DNA copy number (mtDNA-cn), which represents the number of mitochondrial genomes per cell, can be quantified in peripheral blood mononuclear cells (PBMC) and is thought to reflect variations in mitochondrial biogenesis. Additionally, mtDNA may be released at low levels into the circulation from mitochondria under cellular stress, resulting in circulating cell-free mtDNA (ccf-mtDNA) detectable in plasma. The source or physiological significance of ccf-mtDNA in psychiatric illness is unknown but may reflect cell damage, cell death, or bioenergetic compromise. Methods: We enrolled suicide attempters (across diagnoses), non-suicidal subjects with Major Depressive Disorder (MDD), and healthy controls (all medication-free) in two independent cohorts (n=110 & n=74). MtDNA was quantified in cell-free plasma and in PBMCs. Results: Ccf-mtDNA was elevated in suicide attempters and in non-suicidal MDD subjects, compared to healthy controls. These group effects were very large (Cohen’s d ranging from 0.9 to 4.0, all p<0.00001). Ccf-mtDNA and cellular PBMC mtDNA-cn were not significantly correlated with each other (r=0.02, p=0.87), suggesting they reflect different processes. Ccf-mtDNA correlated with post-dexamethasone cortisol (r=0.5, p<0.001), suggesting that HPA-axis hyperactivity may be associated with cellular damage and release of ccf-mtDNA into the blood. Ccf-mtDNA also directly correlated with the antioxidant enzyme glutathione peroxidase (r=0.32, p=0.001), possibly reflecting a compensatory attempt to upregulate antioxidant defence mechanisms due to cellular stress. Conclusions: Ccf-mtDNA may represent a novel marker of cellular stress, which is increased in certain psychiatric conditions. These results call for replication in larger cohorts and in longitudinal studies.
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| 2. |
- Lindqvist, Daniel, et al.
(författare)
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Increased Plasma Levels of Circulating Cell-Free Mitochondrial DNS in Suicide Attempters - Associations with HPA-Axis Hyperactivity
- 2017
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Ingår i: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 81:10, s. S228-S228
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Preclinical data suggest that chronic stress may cause cellular damage and mitochondrial dysfunction, potentially leading to the release of mitochondrial DNA (mtDNA) into the bloodstream. Major Depressive Disorder has been associated with an increased amount of mtDNA in leukocytes from saliva samples and blood, but no previous studies have measured plasma levels of free-circulating mtDNA in a clinical psychiatric sample.Methods: In this study, free circulating mtDNA was quantified in plasma samples from 37 suicide attempters, who had undergone a dexamethasone suppression test (DST), and 37 healthy controls. We hypothesized that free circulating mtDNA would be elevated in the suicide attempters and associated with hypothalamic pituitary adrenal (HPA)-axis hyperactivity. Results: Suicide attempters had significantly higher plasma levels of free-circulating mtDNA compared to healthy controls at different time points (pre- and post-DST) (all p-values ,2.98E-12, Cohen’s d ranging from 2.55-4.01). Pre-DST plasma levels of mtDNA were positively correlated with postDST cortisol levels (rho50.49, p,0.003).Conclusions: Suicide attempters may have elevated plasma levels of free-circulating mtDNA, which are related to impaired HPA-axis negative feedback. This peripheral index is consistent with increased cellular or mitochondrial damage. The specific cells and tissues contributing to plasma levels of free-circulating mtDNA are not known, as is the specificity of this finding for suicide attempters. Future studies are needed in order to better understand the relevance of increased freecirculating mtDNA in relation to the pathophysiology underlying suicidal behavior and depression.
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| 3. |
- Massih, Ali R
(författare)
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Electronic transport in pure and doped UO2
- 2017
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Ingår i: Journal of Nuclear Materials. - : Elsevier. - 0022-3115 .- 1873-4820. ; 497, s. 166-182
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Tidskriftsartikel (refereegranskat)abstract
- The thermoelectric properties of pure and doped UO2, namely the thermal and electrical conductivities and the thermopower, are assessed. We adopt the small polaron theory of the Mott type insulators, wherein the charge carriers, the electron and hole on the U3+ and U5+ ions, are treated as small polarons. For the thermal conductivity, the small polaron theory is applicable at temperatures above 1500 K. A review of the experimental data on the temperature dependence of the aforementioned transport properties is made. The data include UO2 with dopants such as Cr2O3, Gd2O3, Y2O3 and Nb2O5. We compare the applications of the theory with the data. Two limiting regimes, adiabatic and nonadiabatic, with the ensuing expressions for the conductivities and the thermoelectric power are considered. We discuss both the merits and shortcomings of the putative small polaron model and the simplification thereof as applied to pure and doped uranium dioxide. (C) 2017 Elsevier B.V. All rights reserved.
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