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Arctic (E22G) mutation in amyloid-β (Aβ enhances Aβ40 fibril accumulation in Alzheimer's disease (AD). Unlike sporadic AD, familial AD (FAD) patients with the mutation exhibit more Aβ40 in the plaque core. However, structural details of E22G Aβ40 fibrils remain elusive, hindering therapeutic progress. Here, we determine a distinctive W-shaped parallel β-sheet structure through co-analysis by cryo-electron microscopy (cryoEM) and solid-state nuclear magnetic resonance (SSNMR) of in-vitro-prepared E22G Aβ40 fibrils. The E22G Aβ40 fibrils displays typical amyloid features in cotton-wool plaques in the FAD, such as low thioflavin-T fluorescence and a less compact unbundled morphology. Furthermore, kinetic and MD studies reveal previously unidentified in-vitro evidence that E22G Aβ40, rather than Aβ42, may trigger Aβ misfolding in the FAD, and prompt subsequent misfolding of wild-type (WT) Aβ40/Aβ42 via cross-seeding. The results provide insight into how the Arctic mutation promotes AD via Aβ40 accumulation and cross-propagation. Here, the authors use cryo-electron microscopy and solid-state NMR in concert to determine a distinctive W-shaped parallel β-sheet structure of in-vitro-prepared E22G Aβ40 fibrils. [ABSTRACT FROM AUTHOR]

Purpose: To clarify the usefulness of optical coherence tomography (OCT) for the objective and quantitative evaluation of retinal nerve fiber layer (RNFL) thickness around the optic disc in a rodent model of nonarteritic ischemic optic neuropathy (rNAION). Methods: Inner retinal thickness was measured using OCT before and after rNAION induction. The thicknesses of the RNFL and the inner plexiform layer (IPL) were measured using a histologic preparation before and 56 days after induction. We compared the inner retinal thickness measured by OCT with that measured by the histologic preparation. Results: The mean inner retinal thickness around the optic disc of normal rats measured using OCT was similar to that measured using a histologic preparation (73.50 ± 4.94 vs. 75.94 ± 5.90 μm). The mean inner retinal thickness of rNAION significantly increased until the 7th day, returned to baseline on the 14th day, and decreased until the 90th day after induction. On the 56th day after rNAION induction, histologic measurements indicated that the mean RNFL thickness had decreased but that the IPL thickness was similar to that at baseline. Conclusion: The mean inner retinal thickness measured by OCT correlated with the RNFL thickness of rNAION. OCT is useful for the objective and quantitative evaluation of RNFL thickness around the optic disc in a model of rNAION. [ABSTRACT FROM AUTHOR]

Purpose: Our aim was to establish a rodent model of nonarteritic ischemic optic neuropathy (rNAION). Methods: To induce rNAION, after administration of Rose Bengal (RB) (2.5 mM), the small vessels of the left optic nerve were photoactivated using a 514-nm argon green laser with about 500-μm spot size for 12 s (RB-laser induction). To evaluate the induction, funduscopic examination, fluorescein angiography (FA), visualization of capillaries within the optic disc, histologic evaluation, and electrophysiological testing were performed. Results: In the RB-laser-induction eyes, the optic disc became swollen on day 3 followed by atrophy on week 8. FA showed filling defects in the choroid and optic disc at an early stage, followed by hyperfluorescence at a late stage. The capillaries within the optic disc were reduced markedly. Histopathologic examination showed acellular nerve fiber layer (NFL) swelling anterior to the optic disc. The morphologic retinal changes were apparent only in the retinal ganglion cell (RGC) layer, with a reduction in the number of cells. Visually evoked potential (VEP) amplitude decreased significantly, but electroretinography (ERG) showed no significant difference. The positive scotopic threshold response (pSTR) was not reduced on the 1st day but was significantly reduced 3 days after induction. Conclusions: The findings are similar to human NAION. Therefore, RB-laser induction is well suited to establish the presence of rNAION. [ABSTRACT FROM AUTHOR]

We developed universal sample holders [the Kochi grid, Kochi clamp, and Okazaki cell) and a transfer vessel (facility-to-facility transfer container (FFTC)] to analyze sensitive and fragile samples, such as extremely small extraterrestrial materials. The holders and container prevent degradation, contamination due to the terrestrial atmosphere (water vapor and oxygen gas) and small particles, as well as mechanical sample damage. The FFTC can isolate the samples from the effects of the atmosphere for more than a week. The Kochi grid and clamp were made for a coordinated micro/nano-analysis that utilizes a focused-ion beam apparatus, transmission electron microscope, and nanoscale secondary ion mass spectrometry. The Okazaki cell was developed as an additional attachment for a scanning transmission X-ray microscope that uses near-edge X-ray absorption fine structure (NEXAFS). These new apparatuses help to minimize possible alterations from the exposure of the samples to air. The coordinated analysis involving these holders was successfully carried out without any sample damage or loss, thereby enabling us to obtain sufficient analytical datasets of textures, crystallography, elemental/isotopic abundances, and molecular functional groups for µm-sized minerals and organics in both the Antarctic micrometeorite and a carbonaceous chondrite. We will apply the coordinated analysis to acquire the complex characteristics in samples obtained by the future spacecraft sample return mission. [ABSTRACT FROM AUTHOR]