Alzheimer's disease pathology and the unfolded protein response : Prospective pathways and therapeutic targets

The authors would like to thank Alzheimer's Research UK (Grant refs: ARUK-PPG2014A-21 and ARUK-NSG2015-1 to BP and DK) who have provided support for relevant projects leading to this review.Peer reviewedPostprin

Fabrication and test of lightweight honeycomb sandwich structures Final report

Fabrication and testing of lightweight honeycomb sandwich structure

Soluble pre-fibrillar tau and β-amyloid species emerge in early human Alzheimer’s disease and track disease progression and cognitive decline

Acknowledgments We would like to gratefully acknowledge all donors and their families for the tissue provided for this study. Human tissue samples were supplied by the Brains for Dementia Research programme, jointly funded by Alzheimer’s Research UK, the Alzheimer’s Society and the Medical Research Council, and sourced from the MRC London Neurodegenerative Diseases Brain Bank, the Manchester Brain Bank, the South West Dementia Brain Bank (SWDBB), the Newcastle Brain Tissue Resource and the Oxford Brain Bank. The Newcastle Brain Tissue Resource and Oxford Brain Bank are also supported by the National Institute for Health Research (NIHR) Units. The South West Dementia Brain Bank (SWDBB) receives additional support from BRACE (Bristol Research into Alzheimer’s and Care of the Elderly). Alz-50, CP13, MC-1 and PHF-1 antibodies were gifted from Dr. Peter Davies and brain lystates from BACE1−/−mice were obtained from Prof Mike Ashford. The work presented here was funded by Alzheimer’s Research UK (Grant refs: ARUKPPG2014A-21 and ARUK-NSG2015-1 to BP and DK and NIH/NIA grants NIH/NINDS R01 NS082730 and R01 AG044372 to NK)Peer reviewedPublisher PD

The Broadband X-Ray Spectrum of the X-Ray-obscured Type 1 AGN 2MASX J193013.80+341049.5

We present results from modeling the broadband X-ray spectrum of the Type 1 active galactic nucleus (AGN) 2MASX J193013.80+341049.5 using NuSTAR, Swift, and archival XMM-Newton observations. We find this source to be highly X-ray obscured, with column densities exceeding 10²³ cm⁻² across all epochs of X-ray observations, spanning an 8 yr period. However, the source exhibits prominent broad optical emission lines, consistent with an unobscured Type 1 AGN classification. We fit the X-ray spectra with both phenomenological reflection models and physically motivated torus models to model the X-ray absorption. We examine the spectral energy distribution of this source and investigate some possible scenarios to explain the mismatch between X-ray and optical classifications. We compare the ratio of reddening to X-ray absorbing column density (E_(B−V)/N_H) and find that 2MASX J193013.80+341049.5 likely has a much lower dust-to-gas ratio relative to the Galactic interstellar medium, suggesting that the broad line region itself could provide the source of extra X-ray obscuration, being composed of low-ionization, dust-free gas

The Complete Infrared View of Active Galactic Nuclei from the 70-month Swift/BAT Catalog

We systematically investigate the near- (NIR) to far-infrared (FIR) photometric properties of a nearly complete sample of local active galactic nuclei (AGN) detected in the Swift/Burst Alert Telescope (BAT) all-sky ultra hard X-ray (14-195 keV) survey. Out of 606 non-blazar AGN in the Swift/BAT 70-month catalog at high galactic latitude of $|b|>10^{\circ}$, we obtain IR photometric data of 604 objects by cross-matching the AGN positions with catalogs from the WISE, AKARI, IRAS, and Herschel infrared observatories. We find a good correlation between the ultra-hard X-ray and mid-IR (MIR) luminosities over five orders of magnitude ($41 < \log (L_{14-195}/{\rm erg}~{\rm s}^{-1})< 46$). Informed by previous measures of the intrinsic spectral energy distribution of AGN, we find FIR pure-AGN candidates whose FIR emission is thought to be AGN-dominated with low starformation activity. We demonstrate that the dust covering factor decreases with the bolometric AGN luminosity, confirming the luminosity-dependent unified scheme. We also show that the completeness of the WISE color-color cut in selecting Swift/BAT AGN increases strongly with 14-195 keV luminosity.Comment: 24 pages, 11 figures, accepted for publication in ApJ. The full list of Table 1 is available at http://www.kusastro.kyoto-u.ac.jp/~ichikawa/table1_MRT.tx

Mutant Tau knock-in mice display frontotemporal dementia relevant behaviour and histopathology

Peer reviewedPostprin

Inflammatory and Angiogenic Protein Detection in the Human Vitreous: Cytometric Bead Assay

Introduction. To evaluate clinical feasibility and reproducibility of cytometric bead assay (CBA) in nondiluted vitreous samples of patients with age-related macular degeneration (ARMD), diabetic macular edema (DME), and central retinal vein occlusion (CRVO). Methods. Twelve patients from a single clinics day qualified for intravitreal injections (ARMD n = 6, DME n = 3, CRVO n = 3) and underwent a combination treatment including a single-site 23 gauge core vitrectomy which yielded a volume of 0.6 mL undiluted vitreous per patient. Interleukin-6 (IL-6), vascular endothelial growth factor isoform A (VEGF-A), and monocyte chemo-attractant protein-1 (MCP-1) were assessed directly from 0.3 mL at the same day (fresh samples). To assess the reproducibility 0.3 ml were frozen for 60 days at −80°, on which the CBA was repeated (frozen samples). Results. In the fresh samples IL-6 was highest in CRVO (median IL-6 55.8 pg/mL) > DME (50.6) > ARMD (3.1). Highest VEGF was measured in CRVO (447.4) > DME (3.9) > ARMD (2.0). MCP-1 was highest in CRVO (595.7) > AMD (530.8) > DME (178). The CBA reproducibility after frozen storage was examined to be most accurate for MCP1 (P = 0.91) > VEGF (P = 0.68) > IL-6 (P = 0.49). Conclusions. CBA is an innovative, fast determining, and reliable technology to analyze proteins in fluids, like the undiluted vitreous, which is important to better understand ocular pathophysiology and pharmacology. There is no influence of intermittent storage at −80° for the reproducibility of the CBA