| 1. |
- Berndt, Sonja I., et al.
(author)
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Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture
- 2013
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:5, s. 501-U69
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Journal article (peer-reviewed)abstract
- Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.
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| 2. |
- Scott, Robert A., et al.
(author)
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Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways
- 2012
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:9, s. 991-1005
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Journal article (peer-reviewed)abstract
- Through genome-wide association meta-analyses of up to 133,010 individuals of European ancestry without diabetes, including individuals newly genotyped using the Metabochip, we have increased the number of confirmed loci influencing glycemic traits to 53, of which 33 also increase type 2 diabetes risk (q < 0.05). Loci influencing fasting insulin concentration showed association with lipid levels and fat distribution, suggesting impact on insulin resistance. Gene-based analyses identified further biologically plausible loci, suggesting that additional loci beyond those reaching genome-wide significance are likely to represent real associations. This conclusion is supported by an excess of directionally consistent and nominally significant signals between discovery and follow-up studies. Functional analysis of these newly discovered loci will further improve our understanding of glycemic control.
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| 3. |
- Arvidson, K., et al.
(author)
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Bone regeneration and stem cells
- 2011
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In: Journal of Cellular and Molecular Medicine (Print). - : Wiley-Blackwell. - 1582-1838 .- 1582-4934. ; 15:4, s. 718-746
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Research review (peer-reviewed)abstract
- Introduction Bone fracture healing and healing problems Biomaterial scaffolds and tissue engineering in bone formation Bone tissue engineering Biomaterial scaffolds Synthetic scaffolds Micro- and nanostructural properties of scaffolds Conclusion Mesenchymal stem cells and osteogenesis Bone tissue Origin of osteoblasts Isolation and characterization of bone marrow derived MSC In vitro differentiation of MSC into osteoblast lineage cells In vivo differentiation of MSC into bone Factors and pathways controlling osteoblast differentiation of hMSC Defining the relationship between osteoblast and adipocyte differentiation from MSC MSC and sex hormones Effect of aging on osteoblastogenesis Conclusion Embryonic, foetal and adult stem cells in osteogenesis Cell-based therapies for bone Specific features of bone cells needed to be advantageous for clinical use Development of therapeutic biological agents Clinical application concerns Conclusion Platelet-rich plasma (PRP), growth factors and osteogenesis PRP effects in vitro on the cells involved in bone repair PRP effects on osteoblasts PRP effects on osteoclasts PRP effects on endothelial cells PRP effects in vivo on experimental animals The clinical use of PRP for bone repair Non-union Distraction osteogenesis Spinal fusion Foot and ankle surgery Total knee arthroplasty Odontostomatology and maxillofacial surgery Conclusion Molecular control of osteogenesis TGF-beta signalling FGF signalling IGF signalling PDGF signalling MAPK signalling pathway Wnt signalling pathway Hedgehog signalling Notch signalling Ephrin signalling Transcription factors regulating osteoblast differentiation Conclusion Summary This invited review covers research areas of central importance for orthopaedic and maxillofacial bone tissue repair, including normal fracture healing and healing problems, biomaterial scaffolds for tissue engineering, mesenchymal and foetal stem cells, effects of sex steroids on mesenchymal stem cells, use of platelet-rich plasma for tissue repair, osteogenesis and its molecular markers. A variety of cells in addition to stem cells, as well as advances in materials science to meet specific requirements for bone and soft tissue regeneration by addition of bioactive molecules, are discussed.
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| 4. |
- Ikram, M. Arfan, et al.
(author)
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Common variants at 6q22 and 17q21 are associated with intracranial volume
- 2012
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:5, s. 539-544
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Journal article (peer-reviewed)abstract
- During aging, intracranial volume remains unchanged and represents maximally attained brain size, while various interacting biological phenomena lead to brain volume loss. Consequently, intracranial volume and brain volume in late life reflect different genetic influences. Our genome-wide association study (GWAS) in 8,175 community-dwelling elderly persons did not reveal any associations at genome-wide significance (P < 5 x 10(-8)) for brain volume. In contrast, intracranial volume was significantly associated with two loci: rs4273712 (P = 3.4 x 10(-11)), a known height-associated locus on chromosome 6q22, and rs9915547 (P = 1.5 x 10(-12)), localized to the inversion on chromosome 17q21. We replicated the associations of these loci with intracranial volume in a separate sample of 1,752 elderly persons (P = 1.1 x 10(-3) for 6q22 and 1.2 x 10(-3) for 17q21). Furthermore, we also found suggestive associations of the 17q21 locus with head circumference in 10,768 children (mean age of 14.5 months). Our data identify two loci associated with head size, with the inversion at 17q21 also likely to be involved in attaining maximal brain size.
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| 5. |
- Khaydukov, Yu. N., et al.
(author)
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Evidence for spin-triplet superconducting correlations in metal-oxide heterostructures with noncollinear magnetization
- 2014
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In: Physical Review B - Condensed Matter and Materials Physics. - 2469-9950 .- 2469-9969. ; 90:3, s. Article no. 035130 -
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Journal article (peer-reviewed)abstract
- Heterostructures composed of ferromagnetic La0.7Sr0.3MnO3, ferromagnetic SrRuO3, and superconducting YBa2Cu3O6+x were studied experimentally. Structures of composition Au/La0.7Sr0.3MnO3/SrRuO3/YBa2Cu3O6+x were prepared by pulsed laser deposition, and their high quality was confirmed by x-ray diffraction and reflectometry. Anoncollinear magnetic state of the heterostructureswas revealed by means of superconducting quantum interference device magnetometry and polarized neutron reflectometry. We have further observed superconducting currents in mesa structures fabricated by deposition of a second superconducting Nb layer on top of the heterostructure, followed by patterning with photolithography and ion-beam etching. Josephson effects observed in these mesa structures can be explained by the penetration of a triplet component of the superconducting order parameter into the magnetic layers.
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| 6. |
- Kilpeläinen, Tuomas O, et al.
(author)
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Physical activity attenuates the influence of FTO variants on obesity risk: a meta-analysis of 218,166 adults and 19,268 children.
- 2011
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In: PLoS medicine. - : Public Library of Science (PLoS). - 1549-1676 .- 1549-1277. ; 8:11
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Journal article (peer-reviewed)abstract
- BACKGROUND: The FTO gene harbors the strongest known susceptibility locus for obesity. While many individual studies have suggested that physical activity (PA) may attenuate the effect of FTO on obesity risk, other studies have not been able to confirm this interaction. To confirm or refute unambiguously whether PA attenuates the association of FTO with obesity risk, we meta-analyzed data from 45 studies of adults (n=218,166) and nine studies of children and adolescents (n=19,268). METHODS AND FINDINGS: All studies identified to have data on the FTO rs9939609 variant (or any proxy [r(2)>0.8]) and PA were invited to participate, regardless of ethnicity or age of the participants. PA was standardized by categorizing it into a dichotomous variable (physically inactive versus active) in each study. Overall, 25% of adults and 13% of children were categorized as inactive. Interaction analyses were performed within each study by including the FTO×PA interaction term in an additive model, adjusting for age and sex. Subsequently, random effects meta-analysis was used to pool the interaction terms. In adults, the minor (A-) allele of rs9939609 increased the odds of obesity by 1.23-fold/allele (95% CI 1.20-1.26), but PA attenuated this effect (p(interaction) =0.001). More specifically, the minor allele of rs9939609 increased the odds of obesity less in the physically active group (odds ratio =1.22/allele, 95% CI 1.19-1.25) than in the inactive group (odds ratio =1.30/allele, 95% CI 1.24-1.36). No such interaction was found in children and adolescents. CONCLUSIONS: The association of the FTO risk allele with the odds of obesity is attenuated by 27% in physically active adults, highlighting the importance of PA in particular in those genetically predisposed to obesity.
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| 7. |
- Ovsyannikov, Gennady, 1948, et al.
(author)
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Triplet superconductivity in oxide ferromagnetic interlayer of mesa-structure
- 2014
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In: Journal of Physics: Conference Series. - : IOP Publishing. - 1742-6588 .- 1742-6596. ; 592:1, s. Art. no. 012136-
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Conference paper (peer-reviewed)abstract
- We present experimental data on Nb-Au/La0.7Sr0.3MnO3/SrRuO3/YBa2Cu3O7-δ mesa- structure with in plane linear size 10÷50 μm. The mesa-structures were patterned from the epitaxial heterostructures fabricated by pulsed laser ablation and magnetron sputtering. Superconducting critical current was observed for mesa-structures with the interlayer thicknesses up to 50 nm. In the mesa-structures with just one, either La0.7Sr0.3MnO3 or SrRuO3 interlayer with a thickness larger than 10 nm no superconducting current was observed. The registered superconducting current for the mesa-structures with a thinner interlayer is attributed to pinholes. Obtained results are discussed in terms of superconducting long-range triplet generation at interfaces of superconductor and a composite ferromagnet consisting of ferromagnetic materials with non-collinear magnetization.
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| 8. |
- Pedersen, Torbjorn O., et al.
(author)
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Endothelial microvascular networks affect gene-expression profiles and osteogenic potential of tissue-engineered constructs
- 2013
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In: STEM CELL RES THER. - : Springer Science and Business Media LLC. - 1757-6512. ; 4, s. 52-
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Journal article (peer-reviewed)abstract
- Introduction: A major determinant of the potential size of cell/scaffold constructs in tissue engineering is vascularization. The aims of this study were twofold: first to determine the in vitro angiogenic and osteogenic geneexpression profiles of endothelial cells (ECs) and mesenchymal stem cells (MSCs) cocultured in a dynamic 3D environment; and second, to assess differentiation and the potential for osteogenesis after in vivo implantation. Methods: MSCs and ECs were grown in dynamic culture in poly(L-lactide-co-1,5-dioxepan-2-one) (poly(LLA-co-DXO)) copolymer scaffolds for 1 week, to generate three-dimensional endothelial microvascular networks. The constructs were then implanted in vivo, in a murine model for ectopic bone formation. Expression of selected genes for angiogenesis and osteogenesis was studied after a 1-week culture in vitro. Human cell proliferation was assessed as expression of ki67, whereas a-smooth muscle actin was used to determine the perivascular differentiation of MSCs. Osteogenesis was evaluated in vivo through detection of selected markers, by using real-time RT-PCR, alkaline phosphatase (ALP), Alizarin Red, hematoxylin/eosin (HE), and Masson trichrome staining. Results: The results show that endothelial microvascular networks could be generated in a poly(LLA-co-DXO) scaffold in vitro and sustained after in vivo implantation. The addition of ECs to MSCs influenced both angiogenic and osteogenic gene-expression profiles. Furthermore, human ki67 was upregulated before and after implantation. MSCs could support functional blood vessels as perivascular cells independent of implanted ECs. In addition, the expression of ALP was upregulated in the presence of endothelial microvascular networks. Conclusions: This study demonstrates that copolymer poly(LLA-co-DXO) scaffolds can be prevascularized with ECs and MSCs. Although a local osteoinductive environment is required to achieve ectopic bone formation, seeding of MSCs with or without ECs increases the osteogenic potential of tissue-engineered constructs.
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| 9. |
- Pedersen, Torbjorn O., et al.
(author)
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Mesenchymal stem cells induce endothelial cell quiescence and promote capillary formation
- 2014
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In: Stem Cell Research & Therapy. - : Springer Science and Business Media LLC. - 1757-6512. ; 5, s. 23-
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Journal article (peer-reviewed)abstract
- Introduction: Rapid establishment of functional blood vessels is a prerequisite for successful tissue engineering. During vascular development, endothelial cells (ECs) and perivascular cells assemble into a complex regulating proliferation of ECs, vessel diameter and production of extracellular matrix proteins. The aim of this study was to evaluate the ability of mesenchymal stem cells (MSCs) to establish an endothelial-perivascular complex in tissue-engineered constructs comprising ECs and MSCs. Methods: Primary human ECs and MSCs were seeded onto poly(L-lactide-co-1,5-dioxepan-2-one) (poly(LLA-co-DXO)) scaffolds and grown in dynamic culture before subcutaneous implantation in immunocompromised mice for 1 and 3 weeks. Cellular activity, angiogenic stimulation and vascular assembly in cell/scaffold constructs seeded with ECs or ECs/MSCs in a 5:1 ratio was monitored with real-time RT-PCR, ELISA and immunohistochemical microscopy analysis. Results: A quiescent phenotype of ECs was generated, by adding MSCs to the culture system. Decreased proliferation of ECs, in addition to up-regulation of selected markers for vascular maturation was demonstrated. Baseline expression of VEGFa was higher for MSCs compared with EC (P < 0.001), with subsequent up-regulated VEGFa-expression for EC/MSC constructs before (P < 0.05) and after implantation (P < 0.01). Furthermore, an inflammatory response with CD11b + cells was generated from implantation of human cells. At the end of the 3 week experimental period, a higher vascular density was shown for both cellular constructs compared with empty control scaffolds (P < 0.01), with the highest density of capillaries being generated in constructs comprising both ECs and MSCs. Conclusions: Induction of a quiescent phenotype of ECs associated with vascular maturation can be achieved by co-seeding with MSCs. Hence, MSCs can be appropriate perivascular cells for tissue-engineered constructs.
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| 10. |
- Petrzhik, A. M., et al.
(author)
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Spin transport in epitaxial magnetic manganite/ruthenate heterostructures with an LaMnO3 layer
- 2014
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In: Journal of Experimental and Theoretical Physics. - : Pleiades Publishing Ltd. - 1090-6509 .- 1063-7761. ; 119:4, s. 745-752
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Journal article (peer-reviewed)abstract
- Epitaxial La0.7Sr0.3MnO3/LaMnO3/SrRuO3 (LSMO/LMO/SRO) heterostructures with an LMO layer 0-35 nm thick are grown by laser ablation on an NdGaO3 substrate at a high temperature. X-ray diffraction and transmission electron microscopy demonstrate sharp interfaces and epitaxial growth of the LSMO and SRO layers in the heterostructures at an LMO layer thickness of 0-35 nm. SQUID measurements of the magnetic moment of the heterostructures with an LMO layer and the data obtained with reflectometry of polarized neutrons show that the manganite LMO layer is a ferromagnet at a temperature below 150 K and strongly affects the magnetic moment of the heterostructures at low temperatures. The magnetoresistance of the mesostructure created from the heterostructure using lithography and ion etching decreases with increasing LMO layer thickness and weakly depends on the direction of an applied magnetic field. If the LMP layer is absent, a negative magnetoresistance is detected; it is likely to be caused by a negative magnetization of the SRO layer.
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