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- Locke, Adam E, et al.
(författare)
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Genetic studies of body mass index yield new insights for obesity biology.
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
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| 3. |
- Attelind, Sofia, et al.
(författare)
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Genetic determinants of apixaban plasma levels and their relationship to bleeding and thromboembolic events
- 2022
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Ingår i: Frontiers in Genetics. - : Frontiers Media S.A.. - 1664-8021. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Apixaban is a direct oral anticoagulant, a factor Xa inhibitor, used for the prevention of ischemic stroke in patients with atrial fibrillation. Despite using recommended dosing a few patients might still experience bleeding or lack of efficacy that might be related to inappropriate drug exposure. We conducted a genome-wide association study using data from 1,325 participants in the pivotal phase three trial of apixaban with the aim to identify genetic factors affecting the pharmacokinetics of apixaban. A candidate gene analysis was also performed for pre-specified variants in ABCB1, ABCG2, CYP3A4, CYP3A5, and SULT1A1, with a subsequent analysis of all available polymorphisms within the candidate genes. Significant findings were further evaluated to assess a potential association with clinical outcome such as bleeding or thromboembolic events. No variant was consistently associated with an altered apixaban exposure on a genome-wide level. The candidate gene analyses showed a statistically significant association with a well-known variant in the drug transporter gene ABCG2 (c.421G > T, rs2231142). Patients carrying this variant had a higher exposure to apixaban [area under the curve (AUC), beta = 151 (95% CI 59-243), p = 0.001]. On average, heterozygotes displayed a 5% increase of AUC and homozygotes a 17% increase of AUC, compared with homozygotes for the wild-type allele. Bleeding or thromboembolic events were not significantly associated with ABCG2 rs2231142. This large genome-wide study demonstrates that genetic variation in the drug transporter gene ABCG2 is associated with the pharmacokinetics of apixaban. However, the influence of this finding on drug exposure was small, and further studies are needed to better understand whether it is of relevance for ischemic and bleeding events.
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| 4. |
- Degerman, Johan, 1976, et al.
(författare)
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An automatic system for in vitro cell migration studies
- 2009
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Ingår i: Journal of Microscopy. - : Wiley. - 0022-2720 .- 1365-2818. ; 233:1, s. 178-191
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Tidskriftsartikel (refereegranskat)abstract
- This paper describes a system for in vitro cell migration analysis. Adult neural stem/progenitor cells are studied using time-lapse bright-field microscopy and thereafter stained immunohistochemically to find and distinguish undifferentiated glial progenitor cells and cells having differentiated into type-1 or type-2 astrocytes. The cells are automatically segmented and tracked through the time-lapse sequence. An extension to the Chan-Vese Level Set segmentation algorithm, including two new terms for specialized growing and pruning, made it possible to resolve clustered cells, and reduced the tracking error by 65%. We used a custom-built manual correction module to form a ground truth used as a reference for tracked cells that could be identified from the fluorescence staining. On average, the tracks were correct 95% of the time, using our new segmentation. The tracking, or association of segmented cells, was performed using a 2-state Hidden Markov Model describing the random behaviour of the cells. By re-estimating the motion model to conform with the segmented data we managed to reduce the number of tracking parameters to essentially only one. Upon characterization of the cell migration by the HMM state occupation function, it was found that glial progenitor cells were moving randomly 2/3 of the time, while the type-2 astrocytes showed a directed movement 2/3 of the time. This finding indicates possibilities for cell-type specific identification and cell sorting of live cells based on specific movement patterns in individual cell populations, which would have valuable applications in neurobiological research.
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| 5. |
- Enarsson, Mia, 1974-
(författare)
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Roles of PDGF for Neural Stem Cells
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Stem cells are endowed with unique qualities: they can both self-renew and give rise to new mature cell types. Central nervous system (CNS) stem cells can give rise to neurons and glia. What factors regulate stem cell fate decisions? Identifying signals that are involved in the regulation of CNS stem cell proliferation, survival, differentiation and migration is fundamental to the understanding of CNS development. In addition, this knowledge hopefully will contribute to more efficient therapies of CNS damages and diseases.The focus of this thesis was to investigate mechanisms of CNS stem cell proliferation and differentiation. We have studied the role for platelet-derived growth factor (PDGF) in these cellular events both in vitro and in vivo. Previous reports have shown that PDGF are implicated in brain tumorigenesis and also supports neuronal differentiation of CNS stem cells. We have found that PDGF promotes survival and proliferation of immature neurons, thereby supporting neuronal differentiation. The intracellular Ras/ERK signaling pathway probably mediates the mitogenic activity of PDGF. In contrast, neuronal differentiation is not dependent on the Ras/ERK pathway. A genetic expression profile of stem cells during their differentiation was obtained. This microarray analysis suggests that PDGF-treated stem cells are at an intermediate stage between proliferation and differentiation. Furthermore, we generated transgenic mice that overexpress Pdgf-b in neural stem cells. Preliminary data indicate no signs of enhanced proliferation of immature neurons. Instead, increased apoptosis was detected in the developing striatum.The results presented in this thesis show how CNS stem cells are regulated by PDGF. PDGFs are widely expressed in the developing CNS and also in some brain tumors, which are thought to arise from CNS stem cells. Thus, this knowledge may contribute to an increased understanding of brain tumorigenesis in addition to normal CNS development.
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| 6. |
- Eriksson, Charli C-G, 1948-, et al.
(författare)
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Academic practice-policy partnerships for health promotion research : experiences from three research programs
- 2014
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Ingår i: Scandinavian Journal of Public Health. - : SAGE Publications. - 1403-4948 .- 1651-1905. ; 42:15 Suppl, s. 88-95
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The development of knowledge for health promotion requires an effective mechanism for collaboration between academics, practitioners, and policymakers. The challenge is better to understand the dynamic and ever-changing context of the researcher-practitioner-policymaker-community relationship.AIMS: The aims were to explore the factors that foster Academic Practice Policy (APP) partnerships, and to systematically and transparently to review three cases.METHODS: Three partnerships were included: Power and Commitment-Alcohol and Drug Prevention by Non-Governmental Organizations in Sweden; Healthy City-Social Inclusion, Urban Governance, and Sustainable Welfare Development; and Empowering Families with Teenagers-Ideals and Reality in Karlskoga and Degerfors. The analysis includes searching for evidence for three hypotheses concerning contextual factors in multi-stakeholder collaboration, and the cumulative effects of partnership synergy.RESULTS: APP partnerships emerge during different phases of research and development. Contextual factors are important; researchers need to be trusted by practitioners and politicians. During planning, it is important to involve the relevant partners. During the implementation phase, time is important. During data collection and capacity building, it is important to have shared objectives for and dialogues about research. Finally, dissemination needs to be integrated into any partnership. The links between process and outcomes in participatory research (PR) can be described by the theory of partnership synergy, which includes consideration of how PR can ensure culturally and logistically appropriate research, enhance recruitment capacity, and generate professional capacity and competence in stakeholder groups. Moreover, there are PR synergies over time.CONCLUSIONS: The fundamentals of a genuine partnership are communication, collaboration, shared visions, and willingness of all stakeholders to learn from one another
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| 10. |
- Eriksson, Karin, 1974-, et al.
(författare)
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Gottfrid Fornanders folkmusiksamling [Musiktryck] : i faksimilutgåva
- 2006
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Bok (övrigt vetenskapligt/konstnärligt)abstract
- Samlingen upptecknades ursprungligen av Gottfrid Fornander (1871-1946) under slutet av 1920-talet och tillhör Dialekt-, ortnamns- och folkminnesarkivet i Göteborg.Den innehåller 225 låtar och visor i olika former, främst dansmusik och en hel del sånger och sånglekar. Gottfrid Fornanders notskrift är vacker, detaljerad och full med anvisningar om allt ifrån tempon till enskilda betoningar och återges därför här i sitt ursprungliga skick. Större delen av låtarna kommer från norra Halland och samlingen utgör ett unikt dokument över den nordhalländska folkmusiken från tiden runt 1900. Uppteckningarna speglar områdets variationsrika spelmansrepertoar och Fornander namnger dessutom ett flertal spelmän, främst från Fjärås, som det sedan tidigare finns få om ens några uppgifter om.Karin Eriksson är riksspelman och fil. dr. i musikvetenskap. År 2004 disputerade hon med avhandlingen ”Bland polskor, gånglåtar och valser. Hallands spelmansförbund och den halländska folkmusiken”, där hon också har undersökt Fornanders folkmusikuppteckningar.
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