| 1. |
- Hibar, Derrek P., et al.
(author)
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Novel genetic loci associated with hippocampal volume
- 2017
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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Journal article (peer-reviewed)abstract
- The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (r(g) = -0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.
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| 2. |
- Satizabal, Claudia L., et al.
(author)
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Genetic architecture of subcortical brain structures in 38,851 individuals
- 2019
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In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:11, s. 1624-
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Journal article (peer-reviewed)abstract
- Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.
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| 3. |
- Dima, Danai, et al.
(author)
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Subcortical volumes across the lifespan : Data from 18,605 healthy individuals aged 3-90 years.
- 2022
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In: Human Brain Mapping. - : Wiley. - 1065-9471 .- 1097-0193. ; 43:1, s. 452-469
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Journal article (peer-reviewed)abstract
- Age has a major effect on brain volume. However, the normative studies available are constrained by small sample sizes, restricted age coverage and significant methodological variability. These limitations introduce inconsistencies and may obscure or distort the lifespan trajectories of brain morphometry. In response, we capitalized on the resources of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to examine age-related trajectories inferred from cross-sectional measures of the ventricles, the basal ganglia (caudate, putamen, pallidum, and nucleus accumbens), the thalamus, hippocampus and amygdala using magnetic resonance imaging data obtained from 18,605 individuals aged 3-90 years. All subcortical structure volumes were at their maximum value early in life. The volume of the basal ganglia showed a monotonic negative association with age thereafter; there was no significant association between age and the volumes of the thalamus, amygdala and the hippocampus (with some degree of decline in thalamus) until the sixth decade of life after which they also showed a steep negative association with age. The lateral ventricles showed continuous enlargement throughout the lifespan. Age was positively associated with inter-individual variability in the hippocampus and amygdala and the lateral ventricles. These results were robust to potential confounders and could be used to examine the functional significance of deviations from typical age-related morphometric patterns.
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| 4. |
- Frangou, Sophia, et al.
(author)
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Cortical thickness across the lifespan : Data from 17,075 healthy individuals aged 3-90 years
- 2022
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In: Human Brain Mapping. - : John Wiley & Sons. - 1065-9471 .- 1097-0193. ; 43:1, s. 431-451
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Journal article (peer-reviewed)abstract
- Delineating the association of age and cortical thickness in healthy individuals is critical given the association of cortical thickness with cognition and behavior. Previous research has shown that robust estimates of the association between age and brain morphometry require large-scale studies. In response, we used cross-sectional data from 17,075 individuals aged 3-90 years from the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to infer age-related changes in cortical thickness. We used fractional polynomial (FP) regression to quantify the association between age and cortical thickness, and we computed normalized growth centiles using the parametric Lambda, Mu, and Sigma method. Interindividual variability was estimated using meta-analysis and one-way analysis of variance. For most regions, their highest cortical thickness value was observed in childhood. Age and cortical thickness showed a negative association; the slope was steeper up to the third decade of life and more gradual thereafter; notable exceptions to this general pattern were entorhinal, temporopolar, and anterior cingulate cortices. Interindividual variability was largest in temporal and frontal regions across the lifespan. Age and its FP combinations explained up to 59% variance in cortical thickness. These results may form the basis of further investigation on normative deviation in cortical thickness and its significance for behavioral and cognitive outcomes.
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| 5. |
- Wingbrant, Helena, et al.
(author)
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MISiCFET chemical sensors for applications in exhaust gases and flue gases
- 2002
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In: Materials Science Forum. - 0255-5476 .- 1662-9752. ; 433-4, s. 953-956
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Journal article (peer-reviewed)abstract
- A chemical gas sensor based on a silicon carbide field effect transistor with a catalytic gate metal has been under development for a number of years. The choice of silicon carbide as the semiconductor material allows the sensor to operate at high temperatures, for more than 6 months in flue gases at 300degreesC and for at least three days at 700degreesC. The chemical inertness of silicon carbide and a buried gate design makes it a suitable sensor technology for applications in corrosive environments such as exhaust gases and flue gases from boilers. The selectivity of the sensor devices is established through the choice of type and structure of the gate metal as well as the operation temperature. In this way NH3 sensors with low cross sensitivity to NOx have been demonstrated as potential sensors for control of selective catalytic reduction (SCR) of NOx by urea injection into diesel exhausts. Here we show that sensors with a porous platinum or iridium gate show different temperature ranges for NH3 detection. The hardness of the silicon carbide makes it for example more resistant to water splash at cold start of a petrol engine than existing technologies, and a sensor which can control the air to fuel ratio, before the exhaust gases are heated, has been demonstrated. Silicon carbide sensors are also tested in flue gases from boilers. Efficient regulation of the combustion in a boiler will decrease fuel consumption and reduce emissions.
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| 6. |
- Andersson, Helena M., et al.
(author)
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Activated protein C cofactor function of protein S: a critical role for Asp95 in the EGF1-like domain
- 2010
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In: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 115:23, s. 4878-4885
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Journal article (peer-reviewed)abstract
- Protein S has an established role in the protein C anticoagulant pathway, where it enhances the factor Va (FVa) and factor VIIIa (FVIIIa) inactivating property of activated protein C (APC). Despite its physiological role and clinical importance, the molecular basis of its action is not fully understood. To clarify the mechanism of the protein S interaction with APC, we have constructed and expressed a library of composite or point variants of human protein S, with residue substitutions introduced into the Gla, thrombin-sensitive region (TSR), epidermal growth factor 1 (EGF1), and EGF2 domains. Cofactor activity for APC was evaluated by calibrated automated thrombography (CAT) using protein S-deficient plasma. Of 27 variants tested initially, only one, protein S D95A (within the EGF1 domain), was largely devoid of functional APC cofactor activity. Protein S D95A was, however, gamma-carboxylated and bound phospholipids with an apparent dissociation constant (Kd(app)) similar to that of wildtype (WT) protein S. In a purified assay using FVa R506Q/R679Q, purified protein S D95A was shown to have greatly reduced ability to enhance APC-induced cleavage of FVa Arg306. It is concluded that residue Asp95 within EGF1 is critical forAPC cofactor function of protein S and could define a principal functional interaction site for APC. (Blood. 2010;115(23):4878-4885)
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| 7. |
- Andersson, Helena M., et al.
(author)
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Differences in the inflammatory plasma cytokine response following two elite female soccer games separated by a 72-h recovery
- 2010
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In: Scandinavian Journal of Medicine and Science in Sports. - Malden, USA : Wiley-Blackwell. - 0905-7188 .- 1600-0838. ; 20:5, s. 740-747
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Journal article (peer-reviewed)abstract
- We investigated changes in a large battery of pro- and anti-inflammatory cytokines in elite female soccer players following two 90-min games separated by a 72-h active or passive recovery. Blood samples were taken from 10 players before, within 15-20 min, 21, 45 and 69 h after the first game and within 15-20 min after the second game. The leukocyte count was analyzed, together with several plasma pro- and anti-inflammatory cytokines, using a multiplex bead array system. After the first and second game, the total leukocytes and neutrophils increased significantly. Likewise, increases (P<0.05) in pro-inflammatory cytokines [interleukin (IL)-12, tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (INF-gamma), IL-17], chemokines [monocyte chemotactic protein-1 (MCP-1), IL-8 and monokine induced by gamma interferon (MIG)], anti-inflammatory cytokines (IL-2R, IL-4, IL-5, IL-7, IL-10, IL-13, INF-alpha) and the mixed cytokine IL-6 were observed. Leukocyte and cytokine levels were normalized within 21 h. Active recovery (low-intensity exercises) did not affect the cytokine responses. A dampened cytokine response was observed after the second game as only IL-12, IL-6, MCP-1, IL-8 and MIG increased (P<0.05). In conclusion, a robust pro- and anti-inflammatory cytokine response occurs after the first but not the second soccer game. The implications of the dampened cytokine response in female players after the second game are unknown.
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| 8. |
- Andersson, Helena M., et al.
(author)
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Elite female soccer players perform more high-intensity running when playing in international games compared with domestic league games
- 2010
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In: Journal of Strength and Conditioning Research. - Philadelphia, USA : Lippincott Williams & Wilkins. - 1064-8011 .- 1533-4287. ; 24:4, s. 912-919
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Journal article (peer-reviewed)abstract
- The purpose of this study was to compare movement pattern, fatigue development, and heart rate (HR) for top-class elite female players when playing international (INT) vs. domestic league games (DOM). Video-based time-motion analyses and HR recordings were performed on 17 players during INT and DOM. The distances covered in high-intensity running (HIR) and sprinting were longer (p < 0.05) in INT compared with DOM. More (p < 0.05) HIR was covered in INT than DOM during first and second half. Additionally, more (p < 0.05) sprinting occurred in INT compared with DOM in the first half. In both game types, the amount of HIR was reduced by 24-27% (p < 0.05) in the last 15-minute period compared with the first four 15-minute periods of the game. The midfielders covered longer (p < 0.05) distances with HIR in INT than in DOM over the entire game and in the most intense 5-minute period of the games, whereas no differences were observed between the game types for defenders. No difference in the HR response was found between INT and DOM. In conclusion, more HIR and sprinting occur in international compared with domestic games, which may affect the fatigue development for players in physically demanding roles. Thus, our results are important to coaches to prepare players to meet the challenges of international soccer games and show that the ability to perform intense intermittent exercise should be trained regularly in elite female players.
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| 9. |
- Andersson, Helena M, et al.
(author)
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Elite football on artificial turf versus natural grass : movement patterns, technical standards, and player impressions
- 2008
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In: Journal of Sports Sciences. - : Informa UK Limited. - 0264-0414 .- 1466-447X. ; 26:2, s. 113-22
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Journal article (peer-reviewed)abstract
- The aim of the present study was to examine the movement patterns, ball skills, and the impressions of Swedish elite football players during competitive games on artificial turf and natural grass. Time - motion analyses (36 observations) and technical analyses (16 team observations) were performed and 72 male and 21 female players completed a questionnaire. No differences were observed between artificial turf and natural grass in terms of total distance covered (mean 10.19 km, s = 0.19 vs. 10.33 km, s = 0.23), high-intensity running (1.86 km, s = 0.10 vs. 1.87 km, s = 0.14), number of sprints (21, s = 1 vs. 22, s = 2), standing tackles (10, s = 1 vs. 11, s = 1) or headers per game (8, s = 1 vs. 8, s = 1), whereas there were fewer sliding tackles (P < 0.05) on artificial turf than natural grass (2.1, s = 0.5 vs. 4.3, s = 0.6). There were more short passes (218, s = 14 vs. 167, s = 12) and midfield-to-midfield passes (148, s = 11 vs. 107, s = 8) (both P < 0.05) on artificial turf than natural grass. On a scale of 0-10, where 0 = "better than", 5 = "equal to", and 10 = "worse than", the male players reported a negative overall impression (8.3, s = 0.2), poorer ball control (7.3, s = 0.3), and greater physical effort (7.2, s = 0.2) on artificial turf than natural grass. In conclusion, the running activities and technical standard were similar during games on artificial turf and natural grass. However, fewer sliding tackles and more short passes were performed during games on artificial turf. The observed change in playing style could partly explain the male players' negative impression of artificial turf.
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| 10. |
- Andersson, Helena M., et al.
(author)
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Plasma antioxidant responses and oxidative stress following a soccer game in elite female players
- 2010
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In: Scandinavian Journal of Medicine and Science in Sports. - Malden, USA : Wiley-Blackwell. - 0905-7188 .- 1600-0838. ; 20:4, s. 600-608
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Journal article (peer-reviewed)abstract
- We aimed to investigate markers of oxidative stress and levels of endogenous and dietary antioxidants in 16 elite female soccer players in response to a 90-min game (average intensity 82+/-3% HRpeak). Blood samples were taken before, immediately and 21 h after the game. Plasma-oxidized glutathione, the ratio of reduced to oxidized glutathione (GSH:GSSG) and lipid peroxidation measured by d-ROMs were used as markers of oxidative stress. Plasma endogenous [uric acid, total glutathione (TGSH)] and dietary antioxidants (alpha-tocopherol, ascorbic acid, total carotenoids and polyphenols) were analyzed using liquid chromatography and the Folin-Ciocalteu method. Exercise induced an acute increase (P<0.05) in GSSG, uric acid, TGSH, alpha-tocopherol, and ascorbic acid. In parallel, the GSH:GSSG ratio and polyphenols decreased (P<0.05). GSSG, GSH:GSSG ratio, uric acid, TGSH, and ascorbic acid returned to baseline at 21 h, while polyphenols and alpha-tocopherol remained altered. Total carotenoids increased above baseline only at 21 h (P<0.05). Lipid peroxidation, measured by d-ROMs, remained unchanged throughout the study. Thus, intermittent exercise in well-trained female athletes induces a transient increase in GSSG and a decrease in the GSH:GSSG ratio, which is effectively balanced by the recruitment of both endogenous and dietary antioxidants, resulting in the absence of lipid peroxidation measured by d-ROMs.
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