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- Rodriguez-Cortez, VC, et al.
(författare)
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Monozygotic twins discordant for common variable immunodeficiency reveal impaired DNA demethylation during naïve-to-memory B-cell transition
- 2015
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6, s. 7335-
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Tidskriftsartikel (refereegranskat)abstract
- Common variable immunodeficiency (CVID), the most frequent primary immunodeficiency characterized by loss of B-cell function, depends partly on genetic defects, and epigenetic changes are thought to contribute to its aetiology. Here we perform a high-throughput DNA methylation analysis of this disorder using a pair of CVID-discordant MZ twins and show predominant gain of DNA methylation in CVID B cells with respect to those from the healthy sibling in critical B lymphocyte genes, such as PIK3CD, BCL2L1, RPS6KB2, TCF3 and KCNN4. Individual analysis confirms hypermethylation of these genes. Analysis in naive, unswitched and switched memory B cells in a CVID patient cohort shows impaired ability to demethylate and upregulate these genes in transitioning from naive to memory cells in CVID. Our results not only indicate a role for epigenetic alterations in CVID but also identify relevant DNA methylation changes in B cells that could explain the clinical manifestations of CVID individuals.
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- Urquiza-González, M., et al.
(författare)
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Benchmark evaluation for a single frequency continuous wave OPO seeded pulsed dye amplifier for high-resolution laser spectroscopy
- 2023
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Ingår i: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE. - 0277-786X .- 1996-756X. - 9781510659032
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Konferensbidrag (refereegranskat)abstract
- The study of the atomic spectrum via resonant laser excitation provides access to underlying effects caused by the nuclear structure, which is of special interest in short-lived radioisotopes produced at Isotope Separator On-Line (ISOL) facilities. Current implementations of resonant laser ionization techniques often limit the extraction of the nuclear observables due to the low spectral resolution of the pulsed laser systems deployed. Several high-resolution spectroscopy techniques demand spectral widths in the order of hundreds of MHz and below. A proven solution to reduce this linewidth is the pulsed amplification of a narrow-band continuous wave (cw) laser. This work presents the demonstration of a pulsed dye amplifier seeded by a commercially available cw Optical Parametric Oscillator (OPO). The performance of this system was compared with competing setups using a cw dye laser seed source as well as a frequency mixing technique using a combination of an injection-locked titanium:sapphire (Ti:Sa) and a Nd:YVO4 laser. Spectral bandwidths of the systems were measured using a high finesse Fabry-Perot Interferometer, resulting in comparable optical linewidths between 140 to 156 MHz at a wavelength of 328 nm for the different laser setups. Suitability for on-line experiments was validated by performing high-resolution spectroscopy of radioactive silver isotopes in the Collinear Resonance Ionization Spectroscopy (CRIS) experiment at the Isotope Separator On-Line Device (ISOLDE), at the European Organization for Nuclear Research (CERN). The quality of the hyperfine spectra was similar for the dye and the OPO seed and the deduced hyperfine splitting was in good agreement with literature, while the frequency mixing technique exhibited less precise results attributed to the frequency instabilities and mode-hops of the single-mode Nd:YVO4 laser.
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- Wallen-Mackenzie, A, et al.
(författare)
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Nurr1-RXR heterodimers mediate RXR ligand-induced signaling in neuronal cells
- 2003
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Ingår i: Genes & development. - : Cold Spring Harbor Laboratory. - 0890-9369 .- 1549-5477. ; 17:24, s. 3036-3047
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Tidskriftsartikel (refereegranskat)abstract
- The retinoid X receptor (RXR) is essential as a common heterodimerization partner of several nuclear receptors (NRs). However, its function as a bona fide receptor for endogenous ligands has remained poorly understood. Such a role would depend on the existence of RXR activating ligands in vivo and on the ability of such ligands to influence relevant biological functions. Here we demonstrate the presence of endogenous RXR ligands in the embryonic central nervous system (CNS) and show that they can activate heterodimers formed between RXR and the orphan NR Nurr1 in vivo. Moreover, RXR ligands increase the number of surviving dopaminergic cells and other neurons in a process mediated by Nurr1-RXR heterodimers. These results provide evidence for a role of Nurr1 as a ligand-independent partner of RXR in its function as a bona fide ligand-activated NR. Finally, our findings identify RXR-Nurr1 heterodimers as a potential target in the treatment of neurodegenerative disease.
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- de Urquiza, AM, et al.
(författare)
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Docosahexaenoic acid, a ligand for the retinoid X receptor in mouse brain
- 2000
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Ingår i: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 290:5499, s. 2140-2144
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Tidskriftsartikel (refereegranskat)abstract
- The retinoid X receptor (RXR) is a nuclear receptor that functions as a ligand-activated transcription factor. Little is known about the ligands that activate RXR in vivo. Here, we identified a factor in brain tissue from adult mice that activates RXR in cell-based assays. Purification and analysis of the factor by mass spectrometry revealed that it is docosahexaenoic acid (DHA), a long-chain polyunsaturated fatty acid that is highly enriched in the adult mammalian brain. Previous work has shown that DHA is essential for brain maturation, and deficiency of DHA in both rodents and humans leads to impaired spatial learning and other abnormalities. These data suggest that DHA may influence neural function through activation of an RXR signaling pathway.
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- Rocklöv, Joacim, Professor, 1979-, et al.
(författare)
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Decision-support tools to build climate resilience against emerging infectious diseases in Europe and beyond
- 2023
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Ingår i: The Lancet Regional Health. - : Elsevier. - 2666-7762. ; 32
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Forskningsöversikt (refereegranskat)abstract
- Climate change is one of several drivers of recurrent outbreaks and geographical range expansion of infectious diseases in Europe. We propose a framework for the co-production of policy-relevant indicators and decision-support tools that track past, present, and future climate-induced disease risks across hazard, exposure, and vulnerability domains at the animal, human, and environmental interface. This entails the co-development of early warning and response systems and tools to assess the costs and benefits of climate change adaptation and mitigation measures across sectors, to increase health system resilience at regional and local levels and reveal novel policy entry points and opportunities. Our approach involves multi-level engagement, innovative methodologies, and novel data streams. We take advantage of intelligence generated locally and empirically to quantify effects in areas experiencing rapid urban transformation and heterogeneous climate-induced disease threats. Our goal is to reduce the knowledge-to-action gap by developing an integrated One Health—Climate Risk framework.
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- Rößling, Guido, et al.
(författare)
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Merging Interactive Visualizations with Hypertextbooks and Course Management
- 2006
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Ingår i: ACM SIGCSE Bulletin: inroads. - New York, New York, USA : ACM Press. - 0097-8418. ; 38:4, s. 166-181
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Tidskriftsartikel (refereegranskat)abstract
- As a report of a working group at ITiCSE 2006, this paper provides a vision of how visualizations and the software that generates them may be integrated into hypertextbooks and course management systems. This integration generates a unique synergy that we call a Visualization-based Computer Science Hypertextbook (VizCoSH). By borrowing features of both traditional hypertextbooks and course management systems, VizCoSHs become delivery platforms that address some of the reasons why visualizations have failed to find widespread use in education. The heart of the paper describes these features and explains, from both a student and teacher perspective, how each feature adds educational value to a visualization. In some cases, this value focuses on pedagogical issues, taking advantage of known strategies for making visualizations more engaging and effective. In other cases, the emphasis is on making it easier for teachers to use visualizations. A set of possible use scenarios and approaches for increasing interest in adopting a VizCoSH are also presented.
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