Physiologically regulated transgenic ABCA1 does not reduce amyloid burden or amyloid‐beta peptide levels in vivo

J Lipid Res. 2007 Apr;48(4):914-23. Epub 2007 Jan 18. Physiologically regulated transgenic ABCA1 does not reduce amyloid burden or amyloid-beta peptide levels in vivo. Hirsch-Reinshagen V, Chan JY, Wilkinson A, Tanaka T, Fan J, Ou G, Maia LF, Singaraja RR, Hayden MR, Wellington CL. Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada. Abstract ABCA1-deficient mice have low levels of poorly lipidated apolipoprotein E (apoE) and exhibit increased amyloid load. To test whether excess ABCA1 protects from amyloid deposition, we crossed APP/PS1 mice to ABCA1 bacterial artificial chromosome (BAC) transgenic mice. Compared with wild-type animals, the ABCA1 BAC led to a 50% increase in cortical ABCA1 protein and a 15% increase in apoE abundance, demonstrating that this BAC supports modest ABCA1 overexpression in brain. However, this was observed only in animals that do not deposit amyloid. Comparison of ABCA1/APP/PS1 mice with APP/PS1 controls revealed no differences in levels of brain ABCA1 protein, amyloid, Abeta, or apoE, despite clear retention of ABCA1 overexpression in the livers of these animals. To further investigate ABCA1 expression in the amyloid-containing brain, we then compared ABCA1 mRNA and protein levels in young and aged cortex and cerebellum of APP/PS1 and ABCA1/APP/PS1 animals. Compared with APP/PS1 controls, aged ABCA1/APP/PS1 mice exhibited increased ABCA1 mRNA, but not protein, selectively in cortex. Additionally, ABCA1 mRNA levels were not increased before amyloid deposition but were induced only in the presence of extensive Abeta and amyloid levels. These data suggest that an induction of ABCA1 expression may be associated with late-stage Alzheimer's neuropathology. PMID: 17235115 [PubMed - indexed for MEDLINE

Annealing Effects on the Band Alignment of ALD SiO2 on (Inx Ga1−x )2 O3 for x = 0.25–0.74

The band alignment of Atomic Layer Deposited SiO 2 on (In x Ga1−x) 2 O 3 at varying indium concentrations is reported before and after annealing at 450 °C and 600 °C to simulate potential processing steps during device fabrication and to determine the thermal stability of MOS structures in high-temperature applications. At all indium concentrations studied, the valence band offsets (VBO) showed a nearly constant decrease as a result of 450 °C annealing. The decrease in VBO was −0.35 eV for (In0.25Ga 0.75) 2 O 3 , −0.45 eV for (In0.42Ga 0.58) 2 O 3 , −0.40 eV for (In0.60Ga 0.40) 2 O 3 , and −0.35 eV (In0.74 Ga0.26) 2 O 3 for 450 °C annealing. After annealing at 600 °C, the band alignment remained stable, with <0.1 eV changes for all structures examined, compared to the offsets after the 450 °C anneal. The band offset shifts after annealing are likely due to changes in bonding at the heterointerface. Even after annealing up to 600 °C, the band alignment remains type I (nested gap) for all indium compositions of (In x Ga1−x ) 2 O 3 studied

Adverse metabolic and mental health outcomes associated with shiftwork in a population-based study of 277,168 workers in UK biobank

Background: Reported associations between shiftwork and health have largely been based on occupation-specific, or single sex studies that might not be generalizable to the entire working population. The objective of this study was to investigate whether shiftwork was independently associated with obesity, diabetes, poor sleep, and well-being in a large, UK general population cohort. Methods: Participants of the UK Biobank study who were employed at the time of assessment were included. Exposure variables were self-reported shiftwork (any shiftwork and night shiftwork); and outcomes were objectively measured obesity, inflammation and physical activity and self-reported lifestyle, sleep and well-being variables, including mental health. Results: Shiftwork was reported by 17% of the 277,168 employed participants. Shiftworkers were more likely to be male, socioeconomically deprived and smokers, and to have higher levels of physical activity. Univariately, and following adjustment for lifestyle and work-related confounders, shiftworkers were more likely to be obese, depressed, to report disturbed sleep, and to have neurotic traits. Conclusions: Shiftwork was independently associated with multiple indicators of poor health and wellbeing, despite higher physical activity, and even in shiftworkers that did not work nights. Shiftwork is an emerging social factor that contributes to disease in the urban environment across the working population

Histo-blood group gene polymorphisms as potential genetic modifiers of infection and cystic fibrosis lung disease severity

Background: The pulmonary phenotype in cystic fibrosis (CF) is variable; thus, environmental and genetic factors likely contribute to clinical heterogeneity. We hypothesized that genetically determined ABO histo-blood group antigen (ABH) differences in glycosylation may lead to differences in microbial binding by airway mucus, and thus predispose to early lung infection and more severe lung disease in a subset of patients with CF. Methods and Principal Findings: Clinical information and DNA was collected on >800 patients with the ΔF508/ΔF508 genotype. Patients in the most severe and mildest quartiles for lung phenotype were enrolled. Blood samples underwent lymphocyte transformation and DNA extraction using standard methods. PCR and sequencing were performed using standard techniques to identify the 9 SNPs required to determine ABO blood type, and to identify the four SNPs that account for 90-95% of Lewis status in Caucasians. Allele identification of the one nonsynonymous SNP in FUT2 that accounts for >95% of the incidence of nonsecretor phenotype in Caucasians was completed using an ABI Taqman assay. The overall prevalence of ABO types, and of FUT2 (secretor) and FUT 3 (Lewis) alleles was consistent with that found in the Caucasian population. There was no difference in distribution of ABH type in the severe versus mild patients, or the age of onset of Pseudomonas aeruginosa infection in the severe or mild groups. Multivariate analyses of other clinical phenotypes, including gender, asthma, and meconium ileus demonstrated no differences between groups based on ABH type. Conclusions and Significance: Polymorphisms in the genes encoding ABO blood type, secretor or Lewis genotypes were not shown to associate with severity of CF lung disease, or age of onset of P. aeruginosa infection, nor was there any association with other clinical phenotypes in a group of 808 patients homozygous for the ΔF508 mutation

Grain refinement of magnesium alloys: a review of recent research, theoretical developments and their application

This paper builds on the ‘‘Grain Refinement of Mg Alloys’’ published in 2005 and reviews the grain refinement research onMg alloys that has been undertaken since then with an emphasis on the theoretical and analytical methods that have been developed. Consideration of recent research results and current theoretical knowledge has highlighted two important factors that affect an alloy’s as-cast grain size. The first factor applies to commercial Mg-Al alloys where it is concluded that impurity and minor elements such as Fe and Mn have a substantially negative impact on grain size because, in combination with Al, intermetallic phases can be formed that tend to poison the more potent native or deliberately added nucleant particles present in the melt. This factor appears to explain the contradictory experimental outcomes reported in the literature and suggests that the search for a more potent and reliable grain refining technology may need to take a different approach. The second factor applies to all alloys and is related to the role of constitutional supercooling which, on the one hand, promotes grain nucleation and, on the other hand, forms a nucleation-free zone preventing further nucleation within this zone, consequently limiting the grain refinement achievable, particularly in low solute-containing alloys. Strategies to reduce the negative impact of these two factors are discussed. Further, the Interdependence model has been shown to apply to a broad range of casting methods from slow cooling gravity die casting to fast cooling high pressure die casting and dynamic methods such as ultrasonic treatment