Prion Seeding Activities of Mouse Scrapie Strains with Divergent PrPSc Protease Sensitivities and Amyloid Plaque Content Using RT-QuIC and eQuIC

Different transmissible spongiform encephalopathy (TSE)-associated forms of prion protein (e.g. PrPSc) can vary markedly in ultrastructure and biochemical characteristics, but each is propagated in the host. PrPSc propagation involves conversion from its normal isoform, PrPC, by a seeded or templated polymerization mechanism. Such a mechanism is also the basis of the RT-QuIC and eQuIC prion assays which use recombinant PrP (rPrPSen) as a substrate. These ultrasensitive detection assays have been developed for TSE prions of several host species and sample tissues, but not for murine models which are central to TSE pathogenesis research. Here we have adapted RT-QuIC and eQuIC to various murine prions and evaluated how seeding activity depends on glycophosphatidylinositol (GPI) anchoring and the abundance of amyloid plaques and protease-resistant PrPSc (PrPRes). Scrapie brain dilutions up to 10-8 and 10-13 were detected by RT-QuIC and eQuIC, respectively. Comparisons of scrapie-affected wild-type mice and transgenic mice expressing GPI anchorless PrP showed that, although similar concentrations of seeding activity accumulated in brain, the heavily amyloid-laden anchorless mouse tissue seeded more rapid reactions. Next we compared seeding activities in the brains of mice with similar infectivity titers, but widely divergent PrPRes levels. For this purpose we compared the 263K and 139A scrapie strains in transgenic mice expressing P101L PrPC. Although the brains of 263K-affected mice had no immunoblot-detectable PrPRes, RT-QuIC indicated that seeding activity was comparable to that associated with a high-PrPRes strain, 139A. Thus, in this comparison, RT-QuIC seeding activity correlated more closely with infectivity than with PrPRes levels. We also found that eQuIC, which incorporates a PrPSc immunoprecipitation step, detected seeding activity in plasma from wild-type and anchorless PrP transgenic mice inoculated with 22L, 79A and/or RML scrapie strains. Overall, we conclude that these new mouse-adapted prion seeding assays detect diverse types of PrPSc

Enhanced Longevity by Ibuprofen, Conserved in Multiple Species, Occurs in Yeast through Inhibition of Tryptophan Import

The common non-steroidal anti-inflammatory drug ibuprofen has been associated with a reduced risk of some age-related pathologies. However, a general pro-longevity role for ibuprofen and its mechanistic basis remains unclear. Here we show that ibuprofen increased the lifespan of Saccharomyces cerevisiae, Caenorhabditis elegans and Drosophila melanogaster, indicative of conserved eukaryotic longevity effects. Studies in yeast indicate that ibuprofen destabilizes the Tat2p permease and inhibits tryptophan uptake. Loss of Tat2p increased replicative lifespan (RLS), but ibuprofen did not increase RLS when Tat2p was stabilized or in an already long-lived strain background impaired for aromatic amino acid uptake. Concomitant with lifespan extension, ibuprofen moderately reduced cell size at birth, leading to a delay in the G1 phase of the cell cycle. Similar changes in cell cycle progression were evident in a large dataset of replicatively long-lived yeast deletion strains. These results point to fundamental cell cycle signatures linked with longevity, implicate aromatic amino acid import in aging and identify a largely safe drug that extends lifespan across different kingdoms of life.The open access fee for this work was funded through the Texas A&M University Open Access to Knowledge (OAK) Fund

Isamu Noguchi's utopian landscapes: the sculpture of playgrounds and gardens

Color poster with text and image

A comparison of workplace safety perceptions among financial decision-makers of medium- vs. large-size companies. Accident Analysis

a b s t r a c t This study, through a random national survey in the U.S., explored how corporate financial decisionmakers perceive important workplace safety issues as a function of the size of the company for which they worked (medium-vs. large-size companies). Telephone surveys were conducted with 404 U.S. corporate financial decision-makers: 203 from medium-size companies and 201 from large companies. Results showed that the patterns of responding for participants from medium-and large-size companies were somewhat similar. The top-rated safety priorities in resource allocation reported by participants from both groups were overexertion, repetitive motion, and bodily reaction. They believed that there were direct and indirect costs associated with workplace injuries and for every dollar spent improving workplace safety, more than four dollars would be returned. They perceived the top benefits of an effective safety program to be predominately financial in nature -increased productivity and reduced costsand the safety modification participants mentioned most often was to have more/better safety-focused training. However, more participants from large-than medium-size companies reported that "falling on the same level" was the major cause of workers' compensation loss, which is in line with industry loss data. Participants from large companies were more likely to see their safety programs as better than those of other companies in their industries, and those of medium-size companies were more likely to mention that there were no improvements needed for their companies

Age and gender stereotypes: new challenges in a changing workplace and workforce

The current research investigated age and gender stereotypes in relation to adaptive performance. Using methods similar to those used in Schein’s studies (1973, 1975), 496 undergraduate students rated 1 of 7 targets on 6 dimensions of adaptive performance. All of the targets varied in age (25, 40, or 55 years) and gender, except one that was age and gender neutral. The 7th served as a reference group and was an age- and gender-neutral target. Results showed that older targets were perceived as less adaptable across most of the dimensions of adaptability. Further, men and women were perceived differently, but differences were consistent with many prevalent gender stereotypes. Finally, female participants tended to rate all targets more favorably than male participants. Implications for human resources management and future research on stereotypes at work are discussed.