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- Bonham, LW, et al.
(författare)
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Genetic variation across RNA metabolism and cell death gene networks is implicated in the semantic variant of primary progressive aphasia
- 2019
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1, s. 10854-
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Tidskriftsartikel (refereegranskat)abstract
- The semantic variant of primary progressive aphasia (svPPA) is a clinical syndrome characterized by neurodegeneration and progressive loss of semantic knowledge. Unlike many other forms of frontotemporal lobar degeneration (FTLD), svPPA has a highly consistent underlying pathology composed of TDP-43 (a regulator of RNA and DNA transcription metabolism). Previous genetic studies of svPPA are limited by small sample sizes and a paucity of common risk variants. Despite this, svPPA’s relatively homogenous clinicopathologic phenotype makes it an ideal investigative model to examine genetic processes that may drive neurodegenerative disease. In this study, we used GWAS metadata, tissue samples from pathologically confirmed frontotemporal lobar degeneration, and in silico techniques to identify and characterize protein interaction networks associated with svPPA risk. We identified 64 svPPA risk genes that interact at the protein level. The protein pathways represented in this svPPA gene network are critical regulators of RNA metabolism and cell death, such as SMAD proteins and NOTCH1. Many of the genes in this network are involved in TDP-43 metabolism. Contrary to the conventional notion that svPPA is a clinical syndrome with few genetic risk factors, our analyses show that svPPA risk is complex and polygenic in nature. Risk for svPPA is likely driven by multiple common variants in genes interacting with TDP-43, along with cell death,x` working in combination to promote neurodegeneration.
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- Gao, YX, et al.
(författare)
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Mendelian randomization implies no direct causal association between leukocyte telomere length and amyotrophic lateral sclerosis
- 2020
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1, s. 12184-
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Tidskriftsartikel (refereegranskat)abstract
- We employed Mendelian randomization (MR) to evaluate the causal relationship between leukocyte telomere length (LTL) and amyotrophic lateral sclerosis (ALS) with summary statistics from genome-wide association studies (n = ~ 38,000 for LTL and ~ 81,000 for ALS in the European population; n = ~ 23,000 for LTL and ~ 4,100 for ALS in the Asian population). We further evaluated mediation roles of lipids in the pathway from LTL to ALS. The odds ratio per standard deviation decrease of LTL on ALS was 1.10 (95% CI 0.93–1.31, p = 0.274) in the European population and 0.75 (95% CI 0.53–1.07, p = 0.116) in the Asian population. This null association was also detected between LTL and frontotemporal dementia in the European population. However, we found that an indirect effect of LTL on ALS might be mediated by low density lipoprotein (LDL) or total cholesterol (TC) in the European population. These results were robust against extensive sensitivity analyses. Overall, our MR study did not support the direct causal association between LTL and the ALS risk in neither population, but provided suggestive evidence for the mediation role of LDL or TC on the influence of LTL and ALS in the European population.
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- Cubero, M., et al.
(författare)
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Do Halo Nuclei Follow Rutherford Elastic Scattering at Energies Below the Barrier? The Case of 11Li
- 2012
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Ingår i: Physical Review Letters. - 1079-7114 .- 0031-9007. ; 109:26
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Tidskriftsartikel (refereegranskat)abstract
- The first measurement of the elastic scattering of the halo nucleus 11Li and its core 9Li on 208Pb at energies near the Coulomb barrier is presented. The 11Li+208Pb elastic scattering shows a strong reduction with respect to the Rutherford cross section, even at energies well below the barrier and down to very small scattering angles. This drastic change of the elastic differential cross section observed in 11Li+208Pb is the consequence of the halo structure of 11Li, as it is not observed in the elastic scattering of its core 9Li at the same energies. Four-body continuum-discretized coupled-channels calculations, based on a three-body model of the 11Li projectile, are found to explain the measured angular distributions and confirm that the observed reduction is mainly due to the strong Coulomb coupling to the dipole states in the low-lying continuum of 11Li. These calculations suggest the presence of a low-lying dipole resonance in 11Li close to the breakup threshold.
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- Fernandez-Garcia, J. P., et al.
(författare)
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11Li Breakup on 208Pb at Energies Around the Coulomb Barrier
- 2013
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Ingår i: Physical Review Letters. - 1079-7114 .- 0031-9007. ; 110:14
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Tidskriftsartikel (refereegranskat)abstract
- The inclusive breakup for the Li-11 + Pb-208 reaction at energies around the Coulomb barrier has been measured for the first time. A sizable yield of Li-9 following the Li-11 dissociation has been observed, even at energies well below the Coulomb barrier. Using the first-order semiclassical perturbation theory of Coulomb excitation it is shown that the breakup probability data measured at small angles can be used to extract effective breakup energy as well as the slope of B(E1) distribution close to the threshold. Four-body continuum-discretized coupled-channels calculations, including both nuclear and Coulomb couplings between the target and projectile to all orders, reproduce the measured inclusive breakup cross sections and support the presence of a dipole resonance in the Li-11 continuum at low excitation energy.
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- Fernandez-Garcia, J. P., et al.
(författare)
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Li-11 structural information from inclusive break-up measurements
- 2015
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Ingår i: EPJ Web of Conferences. - : EDP Sciences. - 2101-6275 .- 2100-014X. ; 88
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Konferensbidrag (refereegranskat)abstract
- Structure information of Li-11 halo nucleus has been obtained from the inclusive break-up measurements of the Li-11+Pb-208 reactions at energies around the Coulomb barrier (E-lab = 24.3 and 29.8 MeV). The effective break-up energy and the slope of B(E1) distribution close to the threshold have been extracted from the experimental data.
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- Fernandez-Garcia, J. P., et al.
(författare)
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Simultaneous analysis of the elastic scattering and breakup channel for the reaction Li-11+Pb-208 at energies near the Coulomb barrier
- 2015
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Ingår i: Physical Review C - Nuclear Physics. - 2469-9985 .- 2469-9993. ; 92:4
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Tidskriftsartikel (refereegranskat)abstract
- We present a detailed analysis of the elastic scattering and breakup channel for the reaction of Li-11 on Pb-208 at incident laboratory energies of 24.3 and 29.8 MeV, measured at the radioactive ion beam facility of TRIUMF, in Vancouver, Canada. A large yield of Li-9 fragments was detected by four charged particle telescopes in a wide angular range. The experimental angular and energy distributions of these Li-9 fragments have been compared to coupled-reaction-channel and continuum-discretized coupled-channel calculations. The large production of Li-9 fragments at small angles can be explained by considering a direct breakup mechanism, while at medium-large angles a competition between direct breakup and neutron transfer to the continuum of the Pb-208 target was observed.
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