| 101. |
|
|
| 102. |
- Ingason, A, et al.
(författare)
-
Expression analysis in a rat psychosis model identifies novel candidate genes validated in a large case-control sample of schizophrenia
- 2015
-
Ingår i: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 5, s. e656-
-
Tidskriftsartikel (refereegranskat)abstract
- Antagonists of the N-methyl-D-aspartate (NMDA)-type glutamate receptor induce psychosis in healthy individuals and exacerbate schizophrenia symptoms in patients. In this study we have produced an animal model of NMDA receptor hypofunction by chronically treating rats with low doses of the NMDA receptor antagonist MK-801. Subsequently, we performed an expression study and identified 20 genes showing altered expression in the brain of these rats compared with untreated animals. We then explored whether the human orthologs of these genes are associated with schizophrenia in the largest schizophrenia genome-wide association study published to date, and found evidence for association for 4 out of the 20 genes: SF3B1, FOXP1, DLG2 and VGLL4. Interestingly, three of these genes, FOXP1, SF3B1 and DLG2, have previously been implicated in neurodevelopmental disorders.
|
|
| 103. |
|
|
| 104. |
- Konte, B, et al.
(författare)
-
HLA-DQB1 6672G>C (rs113332494) is associated with clozapine-induced neutropenia and agranulocytosis in individuals of European ancestry
- 2021
-
Ingår i: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 11:1, s. 214-
-
Tidskriftsartikel (refereegranskat)abstract
- The atypical antipsychotic clozapine is the only effective medication for treatment-resistant schizophrenia. However, it can also induce serious adverse drug reactions, including agranulocytosis and neutropenia. The mechanism by which it does so is largely unknown, but there is evidence for contributing genetic factors. Several studies identified HLA-DQB1 variants and especially a polymorphism located in HLA-DQB1 (6672G>C, rs113332494) as associated with clozapine-induced agranulocytosis and neutropenia. We analysed the risk allele distribution of SNP rs113332494 in a sample of 1396 controls and 178 neutropenia cases of which 60 developed agranulocytosis. Absolute neutrophil counts of 500/mm3 and 1500/mm3 were used for defining agranulocytosis and neutropenia cases, respectively. We also performed association analyses and analysed local ancestry patterns in individuals of European ancestry, seeking replication and extension of earlier findings. HLA-DQB1 (6672G>C, rs113332494) was associated with neutropenia (OR = 6.20, P = 2.20E−06) and agranulocytosis (OR = 10.49, P = 1.83E−06) in individuals of European ancestry. The association signal strengthened after including local ancestry estimates (neutropenia: OR = 10.38, P = 6.05E−08; agranulocytosis: OR = 16.31, P = 1.39E−06), with effect sizes being considerably larger for agranulocytosis. Using local ancestry estimates for prediction, the sensitivity of rs113332494 increased from 11.28 to 55.64% for neutropenia and from 16.67 to 53.70% for agranulocytosis. Our study further strengthens the evidence implicating HLA-DQB1 in agranulocytosis and neutropenia, suggesting components of the immune system as contributing to this serious adverse drug reaction. Using local ancestry estimates might help in identifying risk variants and improve prediction of haematological adverse effects.
|
|
| 105. |
|
|
| 106. |
|
|
| 107. |
|
|
| 108. |
- Balk, Lennart, et al.
(författare)
-
Widespread episodic thiamine deficiency in Northern Hemisphere wildlife
- 2016
-
Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 6
-
Tidskriftsartikel (refereegranskat)abstract
- Many wildlife populations are declining at rates higher than can be explained by known threats to biodiversity. Recently, thiamine (vitamin B-1) deficiency has emerged as a possible contributing cause. Here, thiamine status was systematically investigated in three animal classes: bivalves, ray-finned fishes, and birds. Thiamine diphosphate is required as a cofactor in at least five life-sustaining enzymes that are required for basic cellular metabolism. Analysis of different phosphorylated forms of thiamine, as well as of activities and amount of holoenzyme and apoenzyme forms of thiaminedependent enzymes, revealed episodically occurring thiamine deficiency in all three animal classes. These biochemical effects were also linked to secondary effects on growth, condition, liver size, blood chemistry and composition, histopathology, swimming behaviour and endurance, parasite infestation, and reproduction. It is unlikely that the thiamine deficiency is caused by impaired phosphorylation within the cells. Rather, the results point towards insufficient amounts of thiamine in the food. By investigating a large geographic area, by extending the focus from lethal to sublethal thiamine deficiency, and by linking biochemical alterations to secondary effects, we demonstrate that the problem of thiamine deficiency is considerably more widespread and severe than previously reported.
|
|
| 109. |
- Bastide, Matthieu F, et al.
(författare)
-
Pathophysiology of L-dopa-induced motor and non-motor complications in Parkinson's disease.
- 2015
-
Ingår i: Progress in Neurobiology. - : Elsevier BV. - 1873-5118 .- 0301-0082. ; 132:Jul 21, s. 96-168
-
Forskningsöversikt (refereegranskat)abstract
- Involuntary movements, or dyskinesia, represent a debilitating complication of levodopa (L-dopa) therapy for Parkinson's disease (PD). L-dopa-induced dyskinesia (LID) are ultimately experienced by the vast majority of patients. In addition, psychiatric conditions often manifested as compulsive behaviours, are emerging as a serious problem in the management of L-dopa therapy. The present review attempts to provide an overview of our current understanding of dyskinesia and other L-dopa-induced dysfunctions, a field that dramatically evolved in the past twenty years. In view of the extensive literature on LID, there appeared a critical need to re-frame the concepts, to highlight the most suitable models, to review the central nervous system (CNS) circuitry that may be involved, and to propose a pathophysiological framework was timely and necessary. An updated review to clarify our understanding of LID and other L-dopa-related side effects was therefore timely and necessary. This review should help in the development of novel therapeutic strategies aimed at preventing the generation of dyskinetic symptoms.
|
|
| 110. |
- Branduardi-Raymont, G., et al.
(författare)
-
Exploring solar-terrestrial interactions via multiple imaging observers
- 2022
-
Ingår i: Experimental astronomy. - : Springer Nature. - 0922-6435 .- 1572-9508. ; 54:2-3, s. 361-390
-
Tidskriftsartikel (refereegranskat)abstract
- How does solar wind energy flow through the Earth's magnetosphere, how is it converted and distributed? is the question we want to address. We need to understand how geomagnetic storms and substorms start and grow, not just as a matter of scientific curiosity, but to address a clear and pressing practical problem: space weather, which can influence the performance and reliability of our technological systems, in space and on the ground, and can endanger human life and health. Much knowledge has already been acquired over the past decades, particularly by making use of multiple spacecraft measuring conditions in situ, but the infant stage of space weather forecasting demonstrates that we still have a vast amount of learning to do. A novel global approach is now being taken by a number of space imaging missions which are under development and the first tantalising results of their exploration will be available in the next decade. In this White Paper, submitted to ESA in response to the Voyage 2050 Call, we propose the next step in the quest for a complete understanding of how the Sun controls the Earth's plasma environment: a tomographic imaging approach comprising two spacecraft in highly inclined polar orbits, enabling global imaging of magnetopause and cusps in soft X-rays, of auroral regions in FUV, of plasmasphere and ring current in EUV and ENA (Energetic Neutral Atoms), alongside in situ measurements. Such a mission, encompassing the variety of physical processes determining the conditions of geospace, will be crucial on the way to achieving scientific closure on the question of solar-terrestrial interactions.
|
|
