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

The effects of temperature and time of first feeding on egg and fry development in Atlantic salmon, salmo salar L.

The first part of this study investigated the effects of varying temperature regimes within the range of 8-22°C on the development and survival of Atlantic salmon (Salmo salar L.) eggs and alevins. The temperature tolerance of eggs was lower than that of alevins: egg mortality increased above 11°C and no eggs survived to eyeing or to hatching at 16 and 14°C, respectively; alevin mortality increased above 16°C and no alevins survived at 22°C. Optimal survivals of eggs and alevins occurred at 8-11°C and 10-14°C, respectively. Subsequent survival at later stages of development was largely determined by survival at earlier stages. Developmental abnormalities among eggs (pin-eyed eggs) and alevins (abnormal hatching and yolk-sac oedema) appeared to be temperature-dependent. Development time in days from fertilisation to eyeing, hatching and maximum alevin wet weight (MAWW) varied inversely with temperature. The sum of degree-days from fertilisation to eyeing and to MAWW was similar at all temperatures, but declined with increasing temperature from eyeing to hatching. The hatching period was similar for all temperatures except 8°C where it was significantly longer. Although alevin size at hatching was not temperature-dependent within the range of 8-12°C, alevin size at MAWW decreased progressively with increasing temperature (10-20°C) during the alevin stage. Fry size at first feeding did not affect their subsequent growth rate or survival. Advanced fry which were fed earliest grew at similar rates to those produced at lower temperatures and attained the greatest weight. Biomass gain was more dependent upon survival than upon mean fish weight. The second part of this study investigated the effects of timing of first feeding on fry growth and survival. Alevins fed prior to final yolk resorption were larger and had lower mortalities than those fed after MAWW. Although the "window" of first feeding opportunity lasted several weeks, delaying feeding beyond MAWW reduced absolute growth. A 5-week delay led to mortalities approaching 60%. However, first feeding can be delayed beyond MAWW for 1-2 weeks at 10°C without adversely affecting subsequent survival or growth rate

Diamond in the rough

How the Furman athletic logo came to b

Knock-in of Human BACE1 Cleaves Murine APP and Reiterates Alzheimer-like PhenoTypes

Footnotes We thank Roemex and the College for Life Science and Medicine at the University of Aberdeen for their generous support. The authors declare no competing financial interests.Peer reviewedPublisher PD

Decreased Specific Star Formation Rates in AGN Host Galaxies

We investigate the location of an ultra-hard X-ray selected sample of AGN from the Swift Burst Alert Telescope (BAT) catalog with respect to the main sequence (MS) of star-forming galaxies using Herschel-based measurements of the star formation rate (SFR) and stellar mass (\mstar) from Sloan Digital Sky Survey (SDSS) photometry where the AGN contribution has been carefully removed. We construct the MS with galaxies from the Herschel Reference Survey and Herschel Stripe 82 Survey using the exact same methods to measure the SFR and \mstar{} as the Swift/BAT AGN. We find a large fraction of the Swift/BAT AGN lie below the MS indicating decreased specific SFR (sSFR) compared to non-AGN galaxies. The Swift/BAT AGN are then compared to a high-mass galaxy sample (COLD GASS), where we find a similarity between the AGN in COLD GASS and the Swift/BAT AGN. Both samples of AGN lie firmly between star-forming galaxies on the MS and quiescent galaxies far below the MS. However, we find no relationship between the X-ray luminosity and distance from the MS. While the morphological distribution of the BAT AGN is more similar to star-forming galaxies, the sSFR of each morphology is more similar to the COLD GASS AGN. The merger fraction in the BAT AGN is much higher than the COLD GASS AGN and star-forming galaxies and is related to distance from the MS. These results support a model in which bright AGN tend to be in high mass star-forming galaxies in the process of quenching which eventually starves the supermassive black hole itself.Comment: 23 pages, 14 figures, Accepted for publication in MNRAS 2015 June 23. In original form 2015 January 2

Clinical applications of Fast Field‐Cycling techniques

Peer reviewedPublisher PD

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

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

Peer reviewedPostprin

Distinctive temporal profiles of detergent-soluble and -insoluble tau and Aβ species in human Alzheimer's disease

Alzheimer's disease (AD) pathology relevant proteins tau and beta-amyloid (Aβ) exist as an array of post-translationally modified and conformationally altered species with varying abundance, solubility and toxicity. Insoluble neurofibrillary tau tangles and Aβ plaques are end-stage AD hallmarks, yet may carry less disease significance compared to soluble species. At present, it is unclear how soluble and insoluble tau and Aβ relate to each other as well as to disease progression. Here, detergent soluble and insoluble fractions generated from post-mortem human temporal lobe samples (Brodmann area 21) were probed for tau and Aβ markers in immuno-dot assays. Measures were quantified according to diagnosis (AD cf. Non-AD), neuropathological severity, and correlated with disease progression (Braak stages). All markers were elevated within AD cases cf. non-AD controls (p &lt; 0.05) independent of solubility. However, when considered according to neuropathological severity, phospho-tau (detected via CP13 and AT8 antibodies) was elevated early within the soluble fraction (p &lt; 0.05 intermediate cf. low severity) and emerged only later within the insoluble fraction (p &lt; 0.05 high cf. low severity). In contrast, PHF1 phospho-tau, TOC1 reactive tau oligomers and amyloid markers rose within the two fractions simultaneously. Independent of solubility, cognitive correlations were observed for tau makers and for fibrillary amyloid (OC), however only soluble total Aβ was significantly correlated with intellectual impairment. Following the exclusion of end-stage cases, only soluble total Aβ remained correlated with cognition. The data indicate differential rates of protein aggregation during AD progression and confirm the disease relevance of early emerging soluble Aβ species.</p

Studies based on the Earley and Wolffer social studies vocabulary tests for grades IV, V, and VI.

Thesis (Ed.M.)--Boston Universit