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| 2. |
- Obers, Niels A., et al.
(författare)
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Quantum gravity phenomenology at the dawn of the multi-messenger era—A review
- 2022
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Ingår i: Progress in Particle and Nuclear Physics. - : Elsevier BV. - 0146-6410 .- 1873-2224. ; 125
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Forskningsöversikt (refereegranskat)abstract
- The exploration of the universe has recently entered a new era thanks to the multi-messenger paradigm, characterized by a continuous increase in the quantity and quality of experimental data that is obtained by the detection of the various cosmic messengers (photons, neutrinos, cosmic rays and gravitational waves) from numerous origins. They give us information about their sources in the universe and the properties of the intergalactic medium. Moreover, multi-messenger astronomy opens up the possibility to search for phenomenological signatures of quantum gravity. On the one hand, the most energetic events allow us to test our physical theories at energy regimes which are not directly accessible in accelerators; on the other hand, tiny effects in the propagation of very high energy particles could be amplified by cosmological distances. After decades of merely theoretical investigations, the possibility of obtaining phenomenological indications of Planck-scale effects is a revolutionary step in the quest for a quantum theory of gravity, but it requires cooperation between different communities of physicists (both theoretical and experimental). This review, prepared within the COST Action CA18108 “Quantum gravity phenomenology in the multi-messenger approach”, is aimed at promoting this cooperation by giving a state-of-the art account of the interdisciplinary expertise that is needed in the effective search of quantum gravity footprints in the production, propagation and detection of cosmic messengers.
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| 4. |
- Wang, Li-San, et al.
(författare)
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Rarity of the Alzheimer Disease-Protective APP A673T Variant in the United States.
- 2015
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Ingår i: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 72:2
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Tidskriftsartikel (refereegranskat)abstract
- Recently, a rare variant in the amyloid precursor protein gene (APP) was described in a population from Iceland. This variant, in which alanine is replaced by threonine at position 673 (A673T), appears to protect against late-onset Alzheimer disease (AD). We evaluated the frequency of this variant in AD cases and cognitively normal controls to determine whether this variant will significantly contribute to risk assessment in individuals in the United States.
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| 6. |
- Choi, Junhong, et al.
(författare)
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2'-O-methylation in mRNA disrupts tRNA decoding during translation elongation
- 2018
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Ingår i: Nature Structural & Molecular Biology. - : Springer Nature. - 1545-9993 .- 1545-9985. ; 25:3, s. 208-216
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Tidskriftsartikel (refereegranskat)abstract
- Chemical modifications of mRNA may regulate many aspects of mRNA processing and protein synthesis. Recently, 2 '-O-methylation of nucleotides was identified as a frequent modification in translated regions of human mRNA, showing enrichment in codons for certain amino acids. Here, using single-molecule, bulk kinetics and structural methods, we show that 2 '-O-methylation within coding regions of mRNA disrupts key steps in codon reading during cognate tRNA selection. Our results suggest that 2 '-O-methylation sterically perturbs interactions of ribosomal-monitoring bases (G530, A1492 and A1493) with cognate codon-anticodon helices, thereby inhibiting downstream GTP hydrolysis by elongation factor Tu (EF-Tu) and A-site tRNA accommodation, leading to excessive rejection of cognate aminoacylated tRNAs in initial selection and proofreading. Our current and prior findings highlight how chemical modifications of mRNA tune the dynamics of protein synthesis at different steps of translation elongation.
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| 8. |
- Choi, Junhong, et al.
(författare)
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N-6-methyladenosine in mRNA disrupts tRNA selection and translation-elongation dynamics
- 2016
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Ingår i: Nature Structural & Molecular Biology. - : Springer Science and Business Media LLC. - 1545-9993 .- 1545-9985. ; 23:2, s. 110-
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Tidskriftsartikel (refereegranskat)abstract
- N-6-methylation of adenosine (forming m(6)A) is the most abundant post-transcriptional modification within the coding region of mRNA, but its role during translation remains unknown. Here, we used bulk kinetic and single-molecule methods to probe the effect of m(6)A in mRNA decoding. Although m(6)A base-pairs with uridine during decoding, as shown by X-ray crystallographic analyses of Thermus thermophilus ribosomal complexes, our measurements in an Escherichia coli translation system revealed that m(6)A modification of mRNA acts as a barrier to tRNA accommodation and translation elongation. The interaction between an m(6)A-modified codon and cognate tRNA echoes the interaction between a near-cognate codon and tRNA, because delay in tRNA accommodation depends on the position and context of m(6)A within codons and on the accuracy level of translation. Overall, our results demonstrate that chemical modification of mRNA can change translational dynamics.
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| 9. |
- Chung, Sharon A., et al.
(författare)
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Differential Genetic Associations for Systemic Lupus Erythematosus Based on Anti-dsDNA Autoantibody Production
- 2011
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 7:3, s. e1001323-
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Tidskriftsartikel (refereegranskat)abstract
- Systemic lupus erythematosus (SLE) is a clinically heterogeneous, systemic autoimmune disease characterized by autoantibody formation. Previously published genome-wide association studies (GWAS) have investigated SLE as a single phenotype. Therefore, we conducted a GWAS to identify genetic factors associated with anti-dsDNA autoantibody production, a SLE-related autoantibody with diagnostic and clinical importance. Using two independent datasets, over 400,000 single nucleotide polymorphisms (SNPs) were studied in a total of 1,717 SLE cases and 4,813 healthy controls. Anti-dsDNA autoantibody positive (anti-dsDNA +, n = 811) and anti-dsDNA autoantibody negative (anti-dsDNA -, n = 906) SLE cases were compared to healthy controls and to each other to identify SNPs associated specifically with these SLE subtypes. SNPs in the previously identified SLE susceptibility loci STAT4, IRF5, ITGAM, and the major histocompatibility complex were strongly associated with anti-dsDNA + SLE. Far fewer and weaker associations were observed for anti-dsDNA - SLE. For example, rs7574865 in STAT4 had an OR for anti-dsDNA + SLE of 1.77 (95% CI 1.57-1.99, p = 2.0E-20) compared to an OR for anti-dsDNA - SLE of 1.26 (95% CI 1.12-1.41, p = 2.4E-04), with (Pheterogeneity)<0.0005. SNPs in the SLE susceptibility loci BANK1, KIAA1542, and UBE2L3 showed evidence of association with anti-dsDNA + SLE and were not associated with anti-dsDNA - SLE. In conclusion, we identified differential genetic associations with SLE based on anti-dsDNA autoantibody production. Many previously identified SLE susceptibility loci may confer disease risk through their role in autoantibody production and be more accurately described as autoantibody propensity loci. Lack of strong SNP associations may suggest that other types of genetic variation or non-genetic factors such as environmental exposures have a greater impact on susceptibility to anti-dsDNA - SLE.
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| 10. |
- Munke, Anna, et al.
(författare)
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Data Descriptor : Coherent diffraction of single Rice Dwarf virus particles using hard X-rays at the Linac Coherent Light Source
- 2016
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Ingår i: Scientific Data. - : Nature Publishing Group. - 2052-4463. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- Single particle diffractive imaging data from Rice Dwarf Virus (RDV) were recorded using the Coherent X-ray Imaging (CXI) instrument at the Linac Coherent Light Source (LCLS). RDV was chosen as it is a wellcharacterized model system, useful for proof-of-principle experiments, system optimization and algorithm development. RDV, an icosahedral virus of about 70 nm in diameter, was aerosolized and injected into the approximately 0.1 mu m diameter focused hard X-ray beam at the CXI instrument of LCLS. Diffraction patterns from RDV with signal to 5.9 angstrom ngstrom were recorded. The diffraction data are available through the Coherent X-ray Imaging Data Bank (CXIDB) as a resource for algorithm development, the contents of which are described here.
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