| 1. |
- Mannion, Niamh M., et al.
(author)
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The RNA-Editing Enzyme ADAR1 Controls Innate Immune Responses to RNA
- 2014
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In: Cell Reports. - : Elsevier BV. - 2211-1247. ; 9:4, s. 1482-1494
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Journal article (peer-reviewed)abstract
- The ADAR RNA-editing enzymes deaminate adenosine bases to inosines in cellular RNAs. Aberrant interferon expression occurs in patients in whom ADAR1 mutations cause Aicardi-Goutieres syndrome (AGS) or dystonia arising from striatal neurodegeneration. Adar1 mutant mouse embryos show aberrant interferon induction and die by embryonic day E12.5. We demonstrate that Adar1 embryonic lethality is rescued to live birth in Adar1; Mavs double mutants in which the antiviral interferon induction response to cytoplasmic double-stranded RNA (dsRNA) is prevented. Aberrant immune responses in Adar1 mutant mouse embryo fibroblasts are dramatically reduced by restoring the expression of editing-active cytoplasmic ADARs. We propose that inosine in cellular RNA inhibits antiviral inflammatory and interferon responses by altering RLR interactions. Transfecting dsRNA oligonucleotides containing inosine-uracil base pairs into Adar1 mutant mouse embryo fibroblasts reduces the aberrant innate immune response. ADAR1 mutations causing AGS affect the activity of the interferon-inducible cytoplasmic isoform more severely than the nuclear isoform.
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| 2. |
- Nellaker, Christoffer, et al.
(author)
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Expression profiling of repetitive elements by melting temperature analysis : variation in HERV-W gag expression across human individuals and tissues
- 2009
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In: BMC Genomics. - : Springer Science and Business Media LLC. - 1471-2164. ; 10, s. 532-
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Journal article (peer-reviewed)abstract
- Background: Human endogenous retroviruses (HERV) constitute approximately 8% of the human genome and have long been considered ""junk"". The sheer number and repetitive nature of these elements make studies of their expression methodologically challenging. Hence, little is known of transcription of genomic regions harboring such elements. Results: Applying a recently developed technique for obtaining high resolution melting temperature data, we examined the frequency distributions of HERV-W gag element into 13 Tm categories in human tissues. Transcripts containing HERV-W gag sequences were expressed in non-random patterns with extensive variations in the expression between both tissues, including different brain regions, and individuals. Furthermore, the patterns of such transcripts varied more between individuals in brain regions than other tissues. Conclusion: Thus, regulated expression of non-coding regions of the human genome appears to include the HERV-W family of repetitive elements. Although it remains to be established whether such expression patterns represent leakage from transcription of functional regions or specific transcription, the current approach proves itself useful for studying detailed expression patterns of repetitive regions.
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| 3. |
- Rubinstein, Yaffa R., et al.
(author)
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The case for open science : rare diseases
- 2020
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In: JAMIA Open. - : Oxford University Press (OUP). - 2574-2531. ; 3:3, s. 472-486
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Research review (peer-reviewed)abstract
- The premise of Open Science is that research and medical management will progress faster if data and knowledge are openly shared. The value of Open Science is nowhere more important and appreciated than in the rare disease (RD) community. Research into RDs has been limited by insufficient patient data and resources, a paucity of trained disease experts, and lack of therapeutics, leading to long delays in diagnosis and treatment. These issues can be ameliorated by following the principles and practices of sharing that are intrinsic to Open Science. Here, we describe how the RD community has adopted the core pillars of Open Science, adding new initiatives to promote care and research for RD patients and, ultimately, for all of medicine. We also present recommendations that can advance Open Science more globally.
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