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- Jia, TY, et al.
(author)
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Epigenome-wide meta-analysis of blood DNA methylation and its association with subcortical volumes: findings from the ENIGMA Epigenetics Working Group
- 2021
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In: Molecular psychiatry. - : Springer Science and Business Media LLC. - 1476-5578 .- 1359-4184. ; 26:8, s. 3884-3895
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Journal article (peer-reviewed)abstract
- DNA methylation, which is modulated by both genetic factors and environmental exposures, may offer a unique opportunity to discover novel biomarkers of disease-related brain phenotypes, even when measured in other tissues than brain, such as blood. A few studies of small sample sizes have revealed associations between blood DNA methylation and neuropsychopathology, however, large-scale epigenome-wide association studies (EWAS) are needed to investigate the utility of DNA methylation profiling as a peripheral marker for the brain. Here, in an analysis of eleven international cohorts, totalling 3337 individuals, we report epigenome-wide meta-analyses of blood DNA methylation with volumes of the hippocampus, thalamus and nucleus accumbens (NAcc)—three subcortical regions selected for their associations with disease and heritability and volumetric variability. Analyses of individual CpGs revealed genome-wide significant associations with hippocampal volume at two loci. No significant associations were found for analyses of thalamus and nucleus accumbens volumes. Cluster-based analyses revealed additional differentially methylated regions (DMRs) associated with hippocampal volume. DNA methylation at these loci affected expression of proximal genes involved in learning and memory, stem cell maintenance and differentiation, fatty acid metabolism and type-2 diabetes. These DNA methylation marks, their interaction with genetic variants and their impact on gene expression offer new insights into the relationship between epigenetic variation and brain structure and may provide the basis for biomarker discovery in neurodegeneration and neuropsychiatric conditions.
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- Judd, N., et al.
(author)
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Cognitive and brain development is independently influenced by socioeconomic status and polygenic scores for educational attainment
- 2020
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 117:22, s. 12411-12418
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Journal article (peer-reviewed)abstract
- Genetic factors and socioeconomic status (SES) inequalities play a large role in educational attainment, and both have been associated with variations in brain structure and cognition. However, genetics and SES are correlated, and no prior study has assessed their neural associations independently. Here we used a polygenic score for educational attainment (EduYears-PGS), as well as SES, in a longitudinal study of 551 adolescents to tease apart genetic and environmental associations with brain development and cognition. Subjects received a structural MRI scan at ages 14 and 19. At both time points, they performed three working memory (WM) tasks. SES and EduYears-PGS were correlated (r = 0.27) and had both common and independent associations with brain structure and cognition. Specifically, lower SES was related to less total cortical surface area and lower WM. EduYears-PGS was also related to total cortical surface area, but in addition had a regional association with surface area in the right parietal lobe, a region related to nonverbal cognitive functions, including mathematics, spatial cognition, and WM. SES, but not EduYears-PGS, was related to a change in total cortical surface area from age 14 to 19. This study demonstrates a regional association of EduYears-PGS and the independent prediction of SES with cognitive function and brain development. It suggests that the SES inequalities, in particular parental education, are related to global aspects of cortical development, and exert a persistent influence on brain development during adolescence.
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- Cornwall, L. A., et al.
(author)
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Authentication and authorization mechanisms for multi-domain grid environments
- 2004
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In: Journal of Grid Computing. - : Springer Science and Business Media LLC. - 1570-7873 .- 1572-9184. ; 2:4, s. 301-311
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Journal article (peer-reviewed)abstract
- This article discusses the authentication and the authorization aspects of security in grid environments spanning multiple administrative domains. Achievements in these areas are presented using the EU DataGrid project as an example implementation. It also gives an outlook on future directions of development.
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- Laure, Erwin, et al.
(author)
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Programming the Grid using gLite
- 2006
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In: Computational Methods in Science and Technology. - 1505-0602. ; 12:1, s. 33-45
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Journal article (other academic/artistic)abstract
- The past few years have seen the creation of the first production level Grid infrastructures that offer their users a dependableservice at an unprecedented scale. Depending on the flavor of middleware services these infrastructures deploy (for instance Condor,gLite, Globus, UNICORE, to name only a few) different interfaces to program the Grid infrastructures are provided. Despite ongoingefforts to standardize Grid service interfaces, there are still significant differences in how applications can interface to a Grid infrastructure.In this paper we describe the middleware (gLite) and services deployed on the EGEE Grid infrastructure and explain how applicationscan interface to them.
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- Laure, Erwin, et al.
(author)
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Programming the grid with glite
- 2006
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In: Computational Methods in Science and Technology. - 1505-0602. ; 12:1, s. 33-45
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Journal article (other academic/artistic)abstract
- The past few years have seen the creation of the first production level Grid infrastructures that offer their users a dependable service at an unprecedented scale. Depending on the flavor of middleware services these infrastructures deploy (for instance Condor, gLite, Globus, UNICORE, to name only a few) different interfaces to program the Grid infrastructures are provided. Despite ongoing efforts to standardize Grid service interfaces, there are still significant differences in how applications can interface to a Grid infrastructure. In this paper we describe the middleware (gLite) and services deployed on the EGEE Grid infrastructure and explain how applications can interface to them.
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- Velthorst, E, et al.
(author)
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Genetic risk for schizophrenia and autism, social impairment and developmental pathways to psychosis
- 2018
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In: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 8:1, s. 204-
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Journal article (peer-reviewed)abstract
- While psychotic experiences (PEs) are assumed to represent psychosis liability, general population studies have not been able to establish significant associations between polygenic risk scores (PRS) and PEs. Previous work suggests that PEs may only represent significant risk when accompanied by social impairment. Leveraging data from the large longitudinal IMAGEN cohort, including 2096 14-year old adolescents that were followed-up to age 18, we tested whether the association between polygenic risk and PEs is mediated by (increasing) impairments in social functioning and social cognitive processes. Using structural equation modeling (SEM) for the subset of participants (n = 643) with complete baseline and follow-up data, we examined pathways to PEs. We found that high polygenic risk for schizophrenia (p = 0.014), reduced brain activity to emotional stimuli (p = 0.009) and social impairments in late adolescence (p < 0.001; controlling for functioning in early adolescence) each independently contributed to the severity of PEs at age 18. The pathway between polygenic risk for autism spectrum disorder and PEs was mediated by social impairments in late adolescence (indirect pathway; p = 0.025). These findings point to multiple direct and indirect pathways to PEs, suggesting that different processes are in play, depending on genetic loading, and environment. Our results suggest that treatments targeting prevention of social impairment may be particularly promising for individuals at genetic risk for autism in order to minimize risk for psychosis.
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9. |
- Bordag, Ljudmila A., et al.
(author)
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Interaction of a rotational motion and an axial flow in small geometries for a Taylor-Couette problem
- 2005
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In: Journal of Fluids and Structures. - Amsterdam : Elsevier. - 0889-9746 .- 1095-8622. ; 20:5, s. 621-641
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Journal article (peer-reviewed)abstract
- We analyze the stability of a Taylor-Couette flow under the imposition of a weak axial flow in the case of a very short cylinder with a narrow annulus gap. We consider an incompressible viscous fluid contained in the narrow gap between two concentric short cylinders, in which the inner cylinder rotates with constant angular velocity. The caps of the cylinders have narrow tubes conically tapering to very narrow slits, allowing an axial flow along the surface of the inner cylinder. The approximated solution for the Taylor-Couette flow for short cylinders was found and used for the stability analysis instead of the precise but bulky solution. The sensitivity of the Taylor-Couette flow to small perturbations and to weak axial flow was studied. We demonstrate that perturbations coming from the axial flow cause the propagation of dispersive waves in the Taylor-Couette flow. While in long cylinders the presence of an axial flow leads to the breaking of axial symmetry, in small cylinders it leads to the breaking of mirror symmetry. The coexistence of a rotation and an axial flow requires that, in addition to the energy and the angular momentum of the flow, the helicity must also be studied. The approximated form for the helicity formula in the case of short cylinders was derived. We found that the axial flow stabilizes the Taylor-Couette flow. The supercritical flow includes a rich variety of vortical structures, including a symmetric pair of Taylor vortices, an anomalous single vortex and quasiperiodic oscillating vortices. Pattern formation was studied at large for rated ranges of azimuthal and axial Reynolds numbers. A region where three branches of different states occur was localized. Numerical simulations in 3-D and in the axisymmetrical case of the model flow are presented, which illustrate the instabilities analyzed.
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