| 1. |
- Mak, Elijah, et al.
(författare)
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In vivo coupling of tau pathology and cortical thinning in Alzheimer's disease
- 2018
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Ingår i: Alzheimer's & dementia (Amsterdam, Netherlands). - : Wiley. - 2352-8729. ; 10, s. 678-687
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The deposition of neurofibrillary tangles in neurodegenerative disorders is associated with neuronal loss on autopsy; however, their in vivo associations with atrophy across the continuum of Alzheimer's disease (AD) remain unclear.Methods: We estimated cortical thickness, tau ([18F]-AV-1451), and amyloid β (Aβ) status ([11C]-PiB) in 47 subjects who were stratified into Aβ- (14 healthy controls and six mild cognitive impairment-Aβ-) and Aβ+ (14 mild cognitive impairment-Aβ+ and 13 AD) groups.Results: Compared with the Aβ- group, tau was increased in widespread regions whereas cortical thinning was restricted to the temporal cortices. Increased tau binding was associated with cortical thinning in each Aβ group. Locally, regional tau was associated with temporoparietal atrophy.Discussion: These findings position tau as a promising therapeutic target. Further studies are needed to elucidate the casual relationships between tau pathology and trajectories of atrophy in AD.
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| 2. |
- O’Brien, Timothy M., et al.
(författare)
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Provenance, U-Pb detrital zircon geochronology, Hf isotopic analyses, and Cr-spinel geochemistry of the northeast Yukon-Koyukuk Basin : Implications for interior basin development and sedimentation in Alaska
- 2018
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Ingår i: Geological Society of America Bulletin. - 0016-7606 .- 1943-2674. ; 130:5-6, s. 825-847
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Tidskriftsartikel (refereegranskat)abstract
- The Yukon-Koyukuk Basin is a large depression that covers ∼118,000 km2 in western interior Alaska and is divided into two subbasins by a volcanic arc assemblage. Interpretations of the depositional setting of the northern Kobuk Koyukuk subbasin vary from a syncollisional forearc basin to a postorogenic successor basin formed by lithospheric extension. New results from sandstones and conglomerates collected from the Kobuk Koyukuk subbasin provide evidence for the timing of basin development, insight into the provenance of coarse siliciclastic sediments, and understanding of the nature of Cretaceous paleogeography and paleodrainage of Arctic Alaska.Early sedimentary rocks of the Kobuk Koyukuk subbasin contain abundant mafic to ultramafic volcanic and plutonic lithic fragments and mafic heavy minerals (e.g., spinel, clinopyroxene, and amphibole). They also contain abundant Middle Triassic to early Late Jurassic zircons (240−160 Ma; peak maximum ca. 200 Ma) that yield highly juvenile Hf isotopic compositions. Geochemistry of chromium spinels (Cr# = 0.17−0.86) suggests crystallization in an immature arc setting that likely developed over mid-ocean-ridge basalt−type crust. These early sediments originated from the mafic and ultramafic rocks of the Angayucham terrane, which was once much more extensive. These results suggest that the Angayucham terrane consists of an obducted Middle Triassic to early Late Jurassic oceanic arc complex that was coeval with oceanic- to continental-margin mafic arc magmatism in the Canadian Cordillera.Our generalized stratigraphy, along with U-Pb ages and Lu-Hf isotope analyses of zircons from sedimentary rocks of the Kobuk Koyukuk subbasin, reflects the tectonic and/or erosional unroofing of the adjacent southern Brooks Range and Ruby terrane. U-Pb ages of detrital zircons collected from the stratigraphically lowest mafic- to ultramafic-rich strata yield maximum depositional ages (107 Ma) that reflect initial erosion of the structurally highest Angayucham terrane and initiation of basin formation and deposition in the late Early Cretaceous. Continued uplift and erosion exposed structurally deeper metamorphic rocks, as revealed by incorporation of low-grade phyllites and eventually higher-grade metamorphic schistose lithic detritus and intermediate-composition (e.g., biotite) to metamorphic (e.g., chloritoid and xenotime) heavy mineral suites into the basin sediments. Differences in detrital zircon signatures between similar-age strata in the Colville foreland basin to the north of the Brooks Range and the Kobuk Koyukuk subbasin indicate that the sediments within the two basins were derived from two different sources, and the Brooks Range orogen acted as a drainage divide during late Early Cretaceous deposition.
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| 3. |
- Seelig, Davis M, et al.
(författare)
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Constitutive activation of alternative nuclear factor kappa B pathway in canine diffuse large B-cell lymphoma contributes to tumor cell survival and is a target of new adjuvant therapies
- 2017
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Ingår i: Leukemia and Lymphoma. - : Informa UK Limited. - 1042-8194 .- 1029-2403. ; 58:7, s. 1702-1710
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Tidskriftsartikel (refereegranskat)abstract
- Activation of the classical nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) pathway is a common molecular event observed in both human and canine diffuse large B-cell lymphoma (DLBCL). Although the oncogenic potential of the alternative NFκB pathway (ANFκBP) has also been recently identified in DLBCL, its precise role in tumor pathogenesis and potential as a treatment target is understudied. We hypothesized that up-regulation of the ANFκBP plays an important role in the proliferation and survival of canine DLBCL cells, and we demonstrate that the ANFκBP is constitutively active in primary canine DLBCL samples and a cell line (CLBL1). We further demonstrate that a small interfering RNA inhibits the activation of the NFκB pathway and induces apoptosis in canine DLBCL cells. In conclusion, the ANFκBP facilitates survival of canine DLBCL cells, and thus, dogs with spontaneous DLBCL can provide a useful large animal model to study therapies targeting the ANFκBP.
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