| 1. |
- Aoyagi, Atsushi, et al.
(författare)
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A beta and tau prion-like activities decline with longevity in the Alzheimer's disease human brain
- 2019
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Ingår i: Science Translational Medicine. - : AMER ASSOC ADVANCEMENT SCIENCE. - 1946-6234 .- 1946-6242. ; 11:490
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Tidskriftsartikel (refereegranskat)abstract
- The hallmarks of Alzheimer's disease (AD) are the accumulation of A beta plaques and neurofibrillary tangles composed of hyperphosphorylated tau. We developed sensitive cellular assays using human embryonic kidney-293T cells to quantify intracellular self-propagating conformers of A beta in brain samples from patients with AD or other neurodegenerative diseases. Postmortem brain tissue from patients with AD had measurable amounts of pathological A beta conformers. Individuals over 80 years of age had the lowest amounts of prion-like A beta and phosphorylated tau. Unexpectedly, the longevity-dependent decrease in self-propagating tau conformers occurred in spite of increasing amounts of total insoluble tau. When corrected for the abundance of insoluble tau, the ability of postmortem AD brain homogenates to induce misfolded tau in the cellular assays showed an exponential decrease with longevity, with a half-life of about one decade over the age range of 37 to 99 years. Thus, our findings demonstrate an inverse correlation between longevity in patients with AD and the abundance of pathological tau conformers. Our cellular assays can be applied to patient selection for clinical studies and the development of new drugs and diagnostics for AD.
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| 2. |
- Condello, Carlo, et al.
(författare)
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Structural heterogeneity and intersubject variability of A beta in familial and sporadic Alzheimer's disease
- 2018
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : NATL ACAD SCIENCES. - 0027-8424 .- 1091-6490. ; 115:4, s. E782-E791
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Tidskriftsartikel (refereegranskat)abstract
- Point mutations in the amyloid-beta (A beta) coding region produce a combination of mutant and WT A beta isoforms that yield unique clinicopathologies in familial Alzheimer's disease (fAD) and cerebral amyloid angiopathy (fCAA) patients. Here, we report a method to investigate the structural variability of amyloid deposits found in fAD, fCAA, and sporadic AD (sAD). Using this approach, we demonstrate that mutant A beta determines WT A beta conformation through prion template-directed misfolding. Using principal component analysis of multiple structure-sensitive fluorescent amyloid-binding dyes, we assessed the conformational variability of A beta deposits in fAD, fCAA, and sAD patients. Comparing many deposits from a given patient with the overall population, we found that intrapatient variability is much lower than interpatient variability for both disease types. In a given brain, we observed one or two structurally distinct forms. When two forms coexist, they segregate between the parenchyma and cerebrovasculature, particularly in fAD patients. Compared with sAD samples, deposits from fAD patients show less intersubject variability, and little overlap exists between fAD and sAD deposits. Finally, we examined whether E22G (Arctic) or E22Q (Dutch) mutants direct the misfolding of WT A beta, leading to fAD-like plaques in vivo. Intracerebrally injecting mutant A beta 40 fibrils into transgenic mice expressing only WT A beta induced the deposition of plaques with many biochemical hallmarks of fAD. Thus, mutant A beta 40 prions induce a conformation of WT A beta similar to that found in fAD deposits. These findings indicate that diverse AD phenotypes likely arise from one or more initial A beta prion conformations, which kinetically dominate the spread of prions in the brain.
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| 3. |
- Horton, Tammy, et al.
(författare)
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Improving nomenclatural consistency: a decade of experience in the World Register of Marine Species
- 2017
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Ingår i: European journal of taxonomy. - : Museum National D'Histoire Naturelle. - 2118-9773. ; 389, s. 1-24
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Tidskriftsartikel (refereegranskat)abstract
- The World Register of Marine species (WoRMS) has been established for a decade. The early history of the database involved compilation of existing global and regional species registers. This aggregation, combined with changes to data types and the changing needs of WoRMS users, has resulted in an evolution of data-entry consistency over time. With the task of aggregating the accepted species names for all marine species approaching completion, our focus has shifted to improving the consistency and quality of data held while keeping pace with the addition of > 2000 new marine species described annually. This paper defines priorities and longer-term aims that promote standardisation within and interoperability among biodiversity databases, provides editors with further information on how to input nomenclatural data in a standardised way and clarifies for users of WoRMS how and why names are represented as they are. We 1) explain the categories of names included; 2) list standard reasons used to explain why a name is considered ‘unaccepted’ or ‘uncertain’; 3) present and explain the more difficult situations encountered; 4) describe categories of sources and notes linked to a taxon; and 5) recommend how type material, type locality and environmental information should be entered.
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| 4. |
- Nowakowska, Sylwia, et al.
(författare)
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Configuring Electronic States in an Atomically Precise Array of Quantum Boxes
- 2016
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Ingår i: Small. - : Wiley-VCH Verlagsgesellschaft. - 1613-6810 .- 1613-6829. ; 12:28, s. 3757-3763
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Tidskriftsartikel (refereegranskat)abstract
- A 2D array of electronically coupled quantum boxes is fabricated by means of on-surface self-assembly assuring ultimate precision of each box. The quantum states embedded in the boxes are configured by adsorbates, whose occupancy is controlled with atomic precision. The electronic interbox coupling can be maintained or significantly reduced by proper arrangement of empty and filled boxes.
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| 5. |
- Nowakowska, Sylwia, et al.
(författare)
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Interplay of weak interactions in the atom-by-atom condensation of xenon within quantum boxes
- 2015
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 21:6, s. 6071-
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Tidskriftsartikel (refereegranskat)abstract
- Condensation processes are of key importance in nature and play a fundamental role in chemistry and physics. Owing to size effects at the nanoscale, it is conceptually desired to experimentally probe the dependence of condensate structure on the number of constituents one by one. Here we present an approach to study a condensation process atom-by-atom with the scanning tunnelling microscope, which provides a direct real-space access with atomic precision to the aggregates formed in atomically defined 'quantum boxes'. Our analysis reveals the subtle interplay of competing directional and nondirectional interactions in the emergence of structure and provides unprecedented input for the structural comparison with quantum mechanical models. This approach focuses on-but is not limited to-the model case of xenon condensation and goes significantly beyond the well-established statistical size analysis of clusters in atomic or molecular beams by mass spectrometry.
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