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- Vogel, Jacob W., et al.
(författare)
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Four distinct trajectories of tau deposition identified in Alzheimer’s disease
- 2021
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 27:5, s. 871-881
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer’s disease (AD) is characterized by the spread of tau pathology throughout the cerebral cortex. This spreading pattern was thought to be fairly consistent across individuals, although recent work has demonstrated substantial variability in the population with AD. Using tau-positron emission tomography scans from 1,612 individuals, we identified 4 distinct spatiotemporal trajectories of tau pathology, ranging in prevalence from 18 to 33%. We replicated previously described limbic-predominant and medial temporal lobe-sparing patterns, while also discovering posterior and lateral temporal patterns resembling atypical clinical variants of AD. These ‘subtypes’ were stable during longitudinal follow-up and were replicated in a separate sample using a different radiotracer. The subtypes presented with distinct demographic and cognitive profiles and differing longitudinal outcomes. Additionally, network diffusion models implied that pathology originates and spreads through distinct corticolimbic networks in the different subtypes. Together, our results suggest that variation in tau pathology is common and systematic, perhaps warranting a re-examination of the notion of ‘typical AD’ and a revisiting of tau pathological staging. © 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.
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| 2. |
- Zhou, XP, et al.
(författare)
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Non-coding variability at the APOE locus contributes to the Alzheimer's risk
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 3310-
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer’s disease (AD) is a leading cause of mortality in the elderly. While the coding change of APOE-ε4 is a key risk factor for late-onset AD and has been believed to be the only risk factor in the APOE locus, it does not fully explain the risk effect conferred by the locus. Here, we report the identification of AD causal variants in PVRL2 and APOC1 regions in proximity to APOE and define common risk haplotypes independent of APOE-ε4 coding change. These risk haplotypes are associated with changes of AD-related endophenotypes including cognitive performance, and altered expression of APOE and its nearby genes in the human brain and blood. High-throughput genome-wide chromosome conformation capture analysis further supports the roles of these risk haplotypes in modulating chromatin states and gene expression in the brain. Our findings provide compelling evidence for additional risk factors in the APOE locus that contribute to AD pathogenesis.
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| 8. |
- Sitar, R J, et al.
(författare)
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Multi-instrument analysis of the ionospheric signatures of a hot flow anomaly occurring on July 24, 1996
- 1998
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Ingår i: JOURNAL OF GEOPHYSICAL RESEARCH-SPACE PHYSICS. ; 103, s. 23357-23372
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Tidskriftsartikel (refereegranskat)abstract
- We present the analysis of a coordinated set of observations from the POLAR ultraviolet imager (UVI), ground magnetometers, incoherent scatter radar, solar wind monitors, and the DMSP satellite, focused on a traveling convection vortex (TCV) event on July 24, 1996. Starting at approximately 1036 UT, ground magnetometers in Greenland and eastern Canada observe pulsations consistent with the passing overhead of a series of TCV field-aligned current pairs. Azimuthal scans by the Sondrestrom incoherent scatter radar located near Kangerlussuaq (formerly Sondrestrom), Greenland, at this time show strong modulation in the strength and direction of ionospheric plasma flow. The magnetometer pulsations grow in magnitude over the next hour, peaking in intensity at 1137 UT. Images from the UVI instrument show a localized intensification of auroral emissions over central and western Greenland at 1139 UT. Subsequent images show the intensification grow in strength and propagate westward (tailward) until approximately 1158 UT, at which time the intensification fades, These observations are consistent with the westward passage of four pairs of TCVs over central Greenland. The intensification of auroral emissions at 1139 UT is associated with the leading vortex of the fourth TCV pair, thought to be the result of an upward field-aligned current. The modulated flow observed by the radar is the result of the strong electric fields associated with the field-aligned current systems responsible for the impulsive TCV as they pass through the field of view of the radar. Measurements taken in the solar wind by the Wind spacecraft suggest that a pressure change triggers the onset of TCV activity. A subsequent sudden change in the orientation of the interplanetary magnetic field produces a hot flow anomaly which forms at the bow shock. We believe that the interaction of the hot flow anomaly with the magnetopause intensified the fourth TCV pair and. produced the associated auroral brightening. DMSP particle data indicate that the TCVs occur on field lines which map to the boundary plasma sheet-low latitude boundary layer interface. The ground observations associated with the hot flow anomaly are the first of their kind and provide a mechanism to tie an interplanetary magnetic field orientation change into the existing theory that TCVs result from a deformation of the magnetopause.
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| 9. |
- Cumnock, J. A., et al.
(författare)
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Interplanetary magnetic field control of theta aurora development
- 2002
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Ingår i: Journal of Geophysical Research. - : American Geophysical Union (AGU). - 0148-0227 .- 2156-2202. ; 107:A7
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Tidskriftsartikel (refereegranskat)abstract
- [1] We ascertain the influence of the B-y component of the interplanetary magnetic field (IMF) on theta aurora evolution. During most cases where a transpolar arc is observed to move across the polar region, and form a theta aurora, there are brief (minutes) southward excursions of IMF B-z, however northward IMF is required prior to theta aurora formation. Observations show that theta aurora can form during strictly northward IMF with its motion consistent with a change in sign of IMF B-y. It is important to note that since transpolar arcs can persist for 20-30 min after the IMF turns southward, errors will occur in assigning instantaneous IMF conditions to snapshots'' of particular auroral patterns. We consider the entire evolution of the theta aurora and the changing IMF conditions. The influence of IMF B-y is best illustrated by examples which occur during steady northward IMF as compared to times when the IMF is northward on average. We show examples, provided by the Polar UV imager, when the IMF is steady northward. For one case, DMSP F13 and F14 provide in situ measurements of precipitating particles, ionospheric plasma flows and ion density. This unique data set enables us to analyze in detail the evolution of a theta aurora, in one case crossing the entire polar region. No sign change in B-z is needed for theta aurora formation.
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| 10. |
- Ogony, Joshua, et al.
(författare)
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Towards defining morphologic parameters of normal parous and nulliparous breast tissues by artificial intelligence
- 2022
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Ingår i: Breast Cancer Research. - : BMC. - 1465-5411 .- 1465-542X. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Breast terminal duct lobular units (TDLUs), the source of most breast cancer (BC) precursors, are shaped by age-related involution, a gradual process, and postpartum involution (PPI), a dramatic inflammatory process that restores baseline microanatomy after weaning. Dysregulated PPI is implicated in the pathogenesis of postpartum BCs. We propose that assessment of TDLUs in the postpartum period may have value in risk estimation, but characteristics of these tissues in relation to epidemiological factors are incompletely described. Methods Using validated Artificial Intelligence and morphometric methods, we analyzed digitized images of tissue sections of normal breast tissues stained with hematoxylin and eosin from donors <= 45 years from the Komen Tissue Bank (180 parous and 545 nulliparous). Metrics assessed by AI, included: TDLU count; adipose tissue fraction; mean acini count/TDLU; mean dilated acini; mean average acini area; mean "capillary" area; mean epithelial area; mean ratio of epithelial area versus intralobular stroma; mean mononuclear cell count (surrogate of immune cells); mean fat area proximate to TDLUs and TDLU area. We compared epidemiologic characteristics collected via questionnaire by parity status and race, using a Wilcoxon rank sum test or Fishers exact test. Histologic features were compared between nulliparous and parous women (overall and by time between last birth and donation [recent birth: <= 5 years versus remote birth: > 5 years]) using multivariable regression models. Results Normal breast tissues of parous women contained significantly higher TDLU counts and acini counts, more frequent dilated acini, higher mononuclear cell counts in TDLUs and smaller acini area per TDLU than nulliparas (all multivariable analyses p < 0.001). Differences in TDLU counts and average acini size persisted for > 5 years postpartum, whereas increases in immune cells were most marked <= 5 years of a birth. Relationships were suggestively modified by several other factors, including demographic and reproductive characteristics, ethanol consumption and breastfeeding duration. Conclusions Our study identified sustained expansion of TDLU numbers and reduced average acini area among parous versus nulliparous women and notable increases in immune responses within five years following childbirth. Further, we show that quantitative characteristics of normal breast samples vary with demographic features and BC risk factors.
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