| 1. |
- Middeldorp, Christel M., et al.
(author)
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The Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia : design, results and future prospects
- 2019
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In: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 34:3, s. 279-300
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Journal article (peer-reviewed)abstract
- The impact of many unfavorable childhood traits or diseases, such as low birth weight and mental disorders, is not limited to childhood and adolescence, as they are also associated with poor outcomes in adulthood, such as cardiovascular disease. Insight into the genetic etiology of childhood and adolescent traits and disorders may therefore provide new perspectives, not only on how to improve wellbeing during childhood, but also how to prevent later adverse outcomes. To achieve the sample sizes required for genetic research, the Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia were established. The majority of the participating cohorts are longitudinal population-based samples, but other cohorts with data on early childhood phenotypes are also involved. Cohorts often have a broad focus and collect(ed) data on various somatic and psychiatric traits as well as environmental factors. Genetic variants have been successfully identified for multiple traits, for example, birth weight, atopic dermatitis, childhood BMI, allergic sensitization, and pubertal growth. Furthermore, the results have shown that genetic factors also partly underlie the association with adult traits. As sample sizes are still increasing, it is expected that future analyses will identify additional variants. This, in combination with the development of innovative statistical methods, will provide detailed insight on the mechanisms underlying the transition from childhood to adult disorders. Both consortia welcome new collaborations. Policies and contact details are available from the corresponding authors of this manuscript and/or the consortium websites.
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| 2. |
- Liu, Ya, 1991, et al.
(author)
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A Novel Graphene Quantum Dot-Based mRNA Delivery Platform
- 2021
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In: ChemistryOpen. - : Wiley. - 2191-1363. ; 10:7, s. 666-671
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Journal article (peer-reviewed)abstract
- During the last decades, there has been growing interest in using therapeutic messager RNA (mRNA) together with drug delivery systems. Naked, unformulated mRNA is, however, unable to cross the cell membrane and is susceptible to degradation. Here we use graphene quantum dots (GQDs) functionalized with polyethyleneimine (PEI) as a novel mRNA delivery system. Our results show that these modified GQDs can be used to deliver intact and functional mRNA to Huh-7 hepatocarcinoma cells at low doses and, that the GQDs are not toxic, although cellular toxicity is a problem for these first-generation modified particles. Functionalized GQDs represent a potentially interesting delivery system that is easy to manufacture, stable and effective.
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| 3. |
- Liu, Johan, 1960, et al.
(author)
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Stem Cell Growth and Migration on Nanofibrous Polymer Scaffolds and Micro-Fluidic Channels on Silicon-Chip
- 2009
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In: Proceedings of the 2009 Electronic Components and Technology Conference. - 0569-5503. - 9781424444762 ; , s. 1080-1085
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Conference paper (peer-reviewed)abstract
- Stem cell growth and migration on nanofibrous scaffolds and micro-fluidic channels on Silicon-Chip were studied by using neural stem cells isolated from adult rats' brain. Electrospinning and lithographic technique were used for developing nanofibrous-polylactic acid (PLA) and polyurethane (PU) based-scaffolds and micro-fluidic channels on Si-Chips respectively. Immunocytochemical and morphological analysis showed better cell-matrix interaction with profound adhesion, proliferation and migration on the developed scaffolds. Cell culture assay with microfluidic channel revealed the ability of developed channel system in guiding neuronal stem cell growth towards specified directions. These studies extend the possibility of using developed nanofibrous scaffolds and micro-fluidic channel system for future electrical signal transmission based on living neural stem cells.
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| 4. |
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| 5. |
- Smith, Jennifer A, et al.
(author)
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Genome-wide association study identifies 74 loci associated with educational attainment
- 2016
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In: Nature (London). - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 533:7604, s. 539-542
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Journal article (peer-reviewed)abstract
- Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals. Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends our earlier discovery sample of 101,069 individuals to 293,723 individuals, and a replication study in an independent sample of 111,349 individuals from the UK Biobank. We identify 74 genome-wide significant loci associated with the number of years of schooling completed. Single-nucleotide polymorphisms associated with educational attainment are disproportionately found in genomic regions regulating gene expression in the fetal brain. Candidate genes are preferentially expressed in neural tissue, especially during the prenatal period, and enriched for biological pathways involved in neural development. Our findings demonstrate that, even for a behavioural phenotype that is mostly environmentally determined, a well-powered GWAS identifies replicable associated genetic variants that suggest biologically relevant pathways. Because educational attainment is measured in large numbers of individuals, it will continue to be useful as a proxy phenotype in efforts to characterize the genetic influences of related phenotypes, including cognition and neuropsychiatric diseases.
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| 6. |
- Zandén, Carl, 1984, et al.
(author)
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Stem cell responses to plasma surface modified electrospun polyurethane scaffolds.
- 2014
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In: Nanomedicine: Nanotechnology, Biology and Medicine. - : Elsevier BV. - 1549-9634 .- 1549-9642. ; 10:5
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Journal article (peer-reviewed)abstract
- The topographical effects from functional materials on stem cell behavior are currently of interest in tissue engineering and regenerative medicine. Here we investigate the influence of argon, oxygen, and hydrogen plasma surface modification of electrospun polyurethane fibers on human embryonic stem cell (hESC) and rat postnatal neural stem cell (NSC) responses. The plasma gases were found to induce three combinations of fiber surface functionalities and roughness textures. On randomly oriented fibers, plasma treatments lead to substantially increased hESC attachment and proliferation as compared to native fibers. Argon plasma was found to induce the most optimal combination of surface functionality and roughness for cell expansion. Contact guided migration of cells and alignment of cell processes were observed on aligned fibers. Neuronal differentiation around 5% was found for all samples and was not significantly affected by the induced variations of surface functional group distribution or individual fiber topography.
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| 7. |
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| 8. |
- Puschmann, Till B., et al.
(author)
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A Novel Method for Three-Dimensional Culture of Central Nervous System Neurons.
- 2014
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In: Tissue engineering. Part C, Methods. - 1937-3392 .- 1937-3384. ; 20:6, s. 485-492
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Journal article (peer-reviewed)abstract
- Neuronal signal transduction and communication in vivo is based on highly complex and dynamic networks among neurons expanding in a three-dimensional (3D) manner. Studies of cell-cell communication, synaptogenesis, and neural network plasticity constitute major research areas for understanding the involvement of neurons in neurodegenerative diseases, such as Huntington's, Alzheimer's, and Parkinson's disease, and in regenerative neural plasticity responses in situations, such as neurotrauma or stroke. Various cell culture systems constitute important experimental platforms to study neuronal functions in health and disease. A major downside of the existing cell culture systems is that the alienating planar cell environment leads to aberrant cell-cell contacts and network formation and increased reactivity of cell culture-contaminating glial cells. To mimic a suitable 3D environment for the growth and investigation of neuronal networks in vitro has posed an insurmountable challenge. Here, we report the development of a novel electrospun, polyurethane nanofiber-based 3D cell culture system for the in vitro support of neuronal networks, in which neurons can grow freely in all directions and form network structures more complex than any culture system has so far been able to support. In this 3D system, neurons extend processes from their cell bodies as a function of the nanofiber diameter. The nanofiber scaffold also minimizes the reactive state of contaminating glial cells.
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| 9. |
- Carlberg, Björn, 1983, et al.
(author)
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Electrospun polyurethane scaffolds for proliferation and neuronal differentiation of human embryonic stem cells.
- 2009
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In: Biomedical materials (Bristol, England). - : IOP Publishing. - 1748-605X .- 1748-6041. ; 4:4
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Journal article (peer-reviewed)abstract
- Adult central nervous system (CNS) tissue has a limited capacity to recover after trauma or disease. Hence, tissue engineering scaffolds intended for CNS repair and rehabilitation have been subject to intense research effort. Electrospun porous scaffolds, mimicking the natural three-dimensional environment of the in vivo extracellular matrix (ECM) and providing physical support, have been identified as promising candidates for CNS tissue engineering. The present study demonstrates in vitro culturing and neuronal differentiation of human embryonic stem cells (hESCs) on electrospun fibrous polyurethane scaffolds. Electrospun scaffolds composed of biocompatible polyurethane resin (Desmopan 9370A, Bayer MaterialScience AG) were prepared with a vertical electrospinning setup. Resulting scaffolds, with a thickness of approximately 150 microm, exhibited high porosity (84%) and a bimodal pore size distribution with peaks at 5-6 and 1 microm. The mean fiber diameter was measured to approximately 360 nm with a standard deviation of 80 nm. The undifferentiated hESC line SA002 (Cellartis AB, Göteborg, Sweden) was seeded and cultured on the produced scaffolds and allowed propagation and then differentiation for up to 47 days. Cultivation of hESC on electrospun fibrous scaffolds proved successful and neuronal differentiation was observed via standard immunocytochemistry. The results indicate that predominantly dopaminergic tyrosine hydroxylase (TH) positive neurons are derived in co-culture with fibrous scaffolds, in comparison to reference cultures under the same differentiation conditions displaying large proportions of GFAP positive cell types. Scanning electron micrographs confirm neurite outgrowth and connection to adjacent cells, as well as cell attachment to individual fibers of the fibrous scaffold. Consequently, electrospun polyurethane scaffolds have been proven feasible as a substrate for hESC propagation and neuronal differentiation. The physical interaction between cells and the fibrous scaffold indicates that these scaffolds provide a three-dimensional physical structure; a potential candidate for neural tissue engineering repair and rehabilitation.
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| 10. |
- Hill, Sandra Malmgren, 1987, et al.
(author)
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Asymmetric Inheritance of Aggregated Proteins and Age Reset in Yeast Are Regulated by Vac17-Dependent Vacuolar Functions
- 2016
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In: Cell Reports. - : Elsevier BV. - 2211-1247. ; 16:3, s. 826-838
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Journal article (peer-reviewed)abstract
- Age can be reset during mitosis in both yeast and stem cells to generate a young daughter cell from an aged and deteriorated one. This phenomenon requires asymmetry-generating genes (AGGs) that govern the asymmetrical inheritance of aggregated proteins. Using a genome-wide imaging screen to identify AGGs in Saccharomyces cerevisiae, we discovered a previously unknown role for endocytosis, vacuole fusion, and the myosin-dependent adaptor protein Vac17 in asymmetrical inheritance of misfolded proteins. Overproduction of Vac17 increases deposition of aggregates into cytoprotective vacuole-associated sites, counteracts age-related breakdown of endocytosis and vacuole integrity, and extends replicative lifespan. The link between damage asymmetry and vesicle trafficking can be explained by a direct interaction between aggregates and vesicles. We also show that the protein disaggregase Hsp104 interacts physically with endocytic vesicle-associated proteins, such as the dynamin-like protein, Vps1, which was also shown to be required for Vac17-dependent sequestration of protein aggregates. These data demonstrate that two physiognomies of aging-reduced endocytosis and protein aggregation-are interconnected and regulated by Vac17.
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