| 1. |
- Bestas, Burcu, et al.
(författare)
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Splice-correcting oligonucleotides restore BTK function in X-linked agammaglobulinemia model
- 2014
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Ingår i: Journal of Clinical Investigation. - 0021-9738 .- 1558-8238. ; 124:9, s. 4067-4081
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Tidskriftsartikel (refereegranskat)abstract
- X-linked agammaglobulinemia (XLA) is an inherited immunodeficiency that results from mutations within the gene encoding Bruton's tyrosine kinase (BTK). Many XLA-associated mutations affect splicing of BTK pre-mRNA and severely impair B cell development. Here, we assessed the potential of antisense, splice-correcting oligonucleotides (SCOs) targeting mutated BTKtranscripts for treating XLA. Both the SCO structural design and chemical properties were optimized using 2'-O-methyl, locked nucleic acid, or phosphorodiamidate morpholino backbones. In order to have access to an animal model of XLA, we engineered a transgenic mouse that harbors a BAC with an authentic, mutated, splice-defective human BTK gene. BTK transgenic mice were bred onto a Btk knockout background to avoid interference of the orthologous mouse protein. Using this model, we determined that BTK-specific SCOs are able to correct aberrantly spliced BTK in B lymphocytes, including pro-B cells. Correction of BTK mRNA restored expression of functional protein, as shown both by enhanced lymphocyte survival and reestablished BTK activation upon B cell receptor stimulation. Furthermore, SCO treatment corrected splicing and restored BTK expression in primary cells from patients with XLA. Together, our data demonstrate that SCOs can restore BTK function and that BTK-targeting SCOs have potential as personalized medicine in patients with XLA.
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| 2. |
- Biague, A, et al.
(författare)
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High sexual risk taking and diverging trends of HIV-1 and HIV-2 in the military of Guinea Bissau
- 2010
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Ingår i: Journal of infection in developing countries. - : Journal of Infection in Developing Countries. - 1972-2680. ; 4:5, s. 301-308
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Tidskriftsartikel (refereegranskat)abstract
- Background: HIV and other sexually transmitted infections are a growing problem in the military personnel of Africa, and information about this problem in Guinea-Bissau is lacking. The aims of this study were to determine the prevalence and trends of the HIV epidemics in the military forces of Guinea Bissau and to explore possible risk factors for HIV infection. Methodology: Repeated cross-sectional surveys of HIV-1 and HIV-2 were conducted between 1992 and 2005, and knowledge, sexual behaviour and risk factors for HIV-1 and HIV-2 in military personnel in Guinea-Bissau were assessed. Results: The seroprevalence of HIV-1, HIV-2 and HIV-1+HIV-2 dual reactivity was 1.1%, 8.4% and 0.1% in 1992-95, and in 2005 7.7%, 5.1% and 1.9%, respectively. Both the increase of HIV-1 and the decline of HIV-2 between 1992-95 and 2005 were significant when adjusted for age (p < 0.001 for both changes). Only a minority did not know how HIV transmits, but sexual risk taking was high. Several significant risk factors were found in univariate analyses for HIV-1 and HIV-2, but the only risk factor that remained significant after multivariate regression analysis was previous contact with a prostitute among HIV-1-positive subjects (single and dually reactive) (p < 0.01). Conclusion: The increasing trend of HIV-1 and the high risky sexual behavior illustrate the need for improvement in HIV/AIDS prevention efforts among military personnel in Guinea Bissau.
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| 3. |
- Guenot, Diego, et al.
(författare)
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Probing electron correlation on the attosecond time scale
- 2014
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Ingår i: High Intensity Lasers and High Field Phenomena, HILAS 2014. - 9781557529954
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Konferensbidrag (refereegranskat)abstract
- We present experimental measurements and theoretical calculations of single and double ionization time delays in various noble gases using an interferometric method. The measured delays allow us to extract information on the electron correlation.
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| 4. |
- Berntsen, Magnus H., et al.
(författare)
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A spin- and angle-resolving photoelectron spectrometer
- 2010
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Ingår i: Review of Scientific Instruments. - : AIP Publishing. - 0034-6748 .- 1089-7623. ; 81:3
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Tidskriftsartikel (refereegranskat)abstract
- A new type of hemispherical electron energy analyzer that permits angle and spin resolved photoelectron spectroscopy has been developed. The analyzer permits standard angle resolved spectra to be recorded with a two-dimensional detector in parallel with spin detection using a mini-Mott polarimeter. General design considerations as well as technical solutions are discussed and test results from the Au(111) surface state are presented.
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| 5. |
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| 6. |
- C. Lin, Yin, et al.
(författare)
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A global network of transcription factors, involving E2A, EBF1 and Foxo1, that orchestrates B cell fate
- 2010
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Ingår i: Nature Immunology. - : Nature Publishing Group. - 1529-2908 .- 1529-2916. ; 11:7, s. 635-U109
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Tidskriftsartikel (refereegranskat)abstract
- It is now established that the transcription factors E2A, EBF1 and Foxo1 have critical roles in B cell development. Here we show that E2A and EBF1 bound regulatory elements present in the Foxo1 locus. E2A and EBF1, as well as E2A and Foxo1, in turn, were wired together by a vast spectrum of cis-regulatory sequences. These associations were dynamic during developmental progression. Occupancy by the E2A isoform E47 directly resulted in greater abundance, as well as a pattern of monomethylation of histone H3 at lysine 4 (H3K4) across putative enhancer regions. Finally, we divided the pro-B cell epigenome into clusters of loci with occupancy by E2A, EBF and Foxo1. From this analysis we constructed a global network consisting of transcriptional regulators, signaling and survival factors that we propose orchestrates B cell fate.
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