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- Abe, K., et al.
(författare)
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J-PARC Neutrino Beamline Upgrade Technical Design Report
- 2019
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Rapport (refereegranskat)abstract
- In this document, technical details of the upgrade plan of the J-PARC neutrino beamline for the extension of the T2K experiment are described. T2K has proposed to accumulate data corresponding to 2×1022 protons-on-target in the next decade, aiming at an initial observation of CP violation with 3σ or higher significance in the case of maximal CP violation. Methods to increase the neutrino beam intensity, which are necessary to achieve the proposed data increase, are described.
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- Beecham, Ashley H, et al.
(författare)
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Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis.
- 2013
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 45:11, s. 1353-60
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Tidskriftsartikel (refereegranskat)abstract
- Using the ImmunoChip custom genotyping array, we analyzed 14,498 subjects with multiple sclerosis and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (P < 1.0 × 10(-4)). In a replication phase, we combined these data with previous genome-wide association study (GWAS) data from an independent 14,802 subjects with multiple sclerosis and 26,703 healthy controls. In these 80,094 individuals of European ancestry, we identified 48 new susceptibility variants (P < 5.0 × 10(-8)), 3 of which we found after conditioning on previously identified variants. Thus, there are now 110 established multiple sclerosis risk variants at 103 discrete loci outside of the major histocompatibility complex. With high-resolution Bayesian fine mapping, we identified five regions where one variant accounted for more than 50% of the posterior probability of association. This study enhances the catalog of multiple sclerosis risk variants and illustrates the value of fine mapping in the resolution of GWAS signals.
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- Chen, J., et al.
(författare)
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Generation of normal T and B lymphocytes by c-jun deficient embryonic stem cells
- 1994
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Ingår i: Immunity. - : Cell Press. - 1074-7613 .- 1097-4180. ; 1:1, s. 65-72
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Tidskriftsartikel (refereegranskat)abstract
- To determine the potential roles of c-jun in lymphocyte development, we generated somatic chimeric mice by injecting homozygous c-jun mutant embryonic stem (ES) cells into blastocysts from recombination activating gene-2 (RAG-2)-deficient mice. Chimeric mice had poor restoration of thymocytes, but contained substantial numbers of mature T and B lymphocytes in the periphery. Stimulation of c-jun-/- B cells resulted in normal levels of proliferation and immunoglobulin secretion. Likewise, stimulation of c-jun-/- T cells resulted in essentially normal levels of IL-2R alpha expression, IL-2 secretion, and proliferation. We further showed that the relatively normal activation responses of the c-jun-/- T cells probably results from the fact that other members of the Jun family contribute to the bulk of the activator protein-1 (AP-1) complexes in normal T cells and, as a result, AP-1 complexes are found at relatively normal levels in c-jun-/- T cells.
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- Ulrich, Jason D., et al.
(författare)
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ApoE facilitates the microglial response to amyloid plaque pathology
- 2018
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Ingår i: Journal of Experimental Medicine. - : ROCKEFELLER UNIV PRESS. - 0022-1007 .- 1540-9538. ; 215:4, s. 1047-1058
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Tidskriftsartikel (refereegranskat)abstract
- One of the hallmarks of Alzheimers disease is the presence of extracellular diffuse and fibrillar plaques predominantly consisting of the amyloid-beta (A beta) peptide. Apolipoprotein E (ApoE) influences the deposition of amyloid pathology through affecting the clearance and aggregation of monomeric A beta in the brain. In addition to influencing A beta metabolism, increasing evidence suggests that apoE influences microglial function in neurodegenerative diseases. Here, we characterize the impact that apoE has on amyloid pathology and the innate immune response in APPPS1 Delta E9 and APPPS1-21 transgenic mice. We report that Apoe deficiency reduced fibrillar plaque deposition, consistent with previous studies. However, fibrillar plaques in Apoe-deficient mice exhibited a striking reduction in plaque compaction. Hyperspectral fluorescent imaging using luminescent conjugated oligothiophenes identified distinct A beta morphotypes in Apoe-deficient mice. We also observed a significant reduction in fibrillar plaque-associated microgliosis and activated microglial gene expression in Apoe-deficient mice, along with significant increases in dystrophic neurites around fibrillar plaques. Our results suggest that apoE is critical in stimulating the innate immune response to amyloid pathology.
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