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Prion diseases (transmissible spongiform encephalopathies) are fatal neurodegenerative diseases, including Creutzfeldt-Jakob disease in humans, scrapie in sheep and bovine spongiform encephalopathy in cattle. While genome-wide association studies in human and quantitative trait loci mapping in mice have provided evidence for multiple susceptibility genes, few of these have been confirmed functionally. Phenotyping mouse models is generally the method of choice. However, this is not a feasible option where many novel genes, without pre-existing models, would need to be tested. We have therefore developed and applied an in-vitro screen to triage and prioritize candidate modifier genes for more detailed future studies which is faster, far more cost effective and ethical relative to mouse bioassay models. An in vitro prion bioassay, the scrapie cell assay, uses a neuroblastoma-derived cell line (PK1) that is susceptible to RML prions and able to propagate prions at high levels. In this study, we have generated stable gene silencing and/or overexpressing PK1-derived cell lines to test whether perturbation of 14 candidate genes affects prion susceptibility. While no consistent differences were determined for seven genes, highly significant changes were detected for Zbtb38, Sorcs1, Stmn2, Hspa13, Fkbp9, Actr10 and Plg, suggesting that they play key roles in the fundamental processes of prion propagation or clearance. Many neurodegenerative diseases involve the accumulation of misfolded protein aggregates and ‘prion-like’ seeding and spread has been implicated in their pathogenesis. It is therefore expected that some of these prion-modifier genes may be of wider relevance in neurodegeneration.

Little information exists on the status of pelagic shark populations in the Atlantic Ocean, especially in the Gulf of Mexico and Caribbean Sea. We derived indices of relative abundance for pelagic sharks based on mandatory logbooks and observer reports from a scientific observer program of the United States (US) pelagic longline fleet. Time series data from the pelagic longline logbook program (1986)(1987)(1988)(1989)(1990)(1991)(1992)(1993)(1994)(1995)(1996)(1997)(1998)(1999)(2000)(2001)(2002)(2003)(2004)(2005) and the pelagic longline observer program (1992)(1993)(1994)(1995)(1996)(1997)(1998)(1999)(2000)(2001)(2002)(2003)(2004)(2005) were standardized with Generalized Linear Model (GLM) procedures. Declines in relative abundance for the 6 pelagic shark species or genera examined in the logbook data analysis ranged from 43% for make sharks, Isurus spp., to 88% for blue sharks, Prionoce g/auca, whereas declines in relative abundance obtained from the observer data analysis were less accentuated than those in the logbook data analysis, with the trend being positive for night sharks, Carcharhinus signatus, and thresher sharks, Alopias spp. There was no significant change in the fork length at capture over the time period considered for blue sharks, shortfin makes Isurus oxyrinchus, or night sharks. The trends obtained must be viewed cautiously given recognized shortcomings, especially of the logbook dataset, and the highly migratory nature of pelagic sharks, which requires a more comprehensive evaluation of trends throughout their range.RESUMEN Existe poca informaci6n sobre el estado de las poblaciones de tiburones pel~gicos en el Oc~o AtImtico, especialmente en el Golfo de M6xico y el Mar Caribe. Derivarnos Indices de abundancia relativa para tiburones pel~gicos a partir de cuademos de biili:ora e informes de observadores de un prograrna de observadores cientlficos de la flota palangrera peJagica de los Estados Unidos (BE.UU.). Las series temporales del prograrna de cuademos de bit&:ora de palangre peJagico (1986)(1987)(1988)(1989)(1990)(1991)(1992)(1993)(1994)(1995)(1996)(1997)(1998)(1999)(2000)(2001)(2002)(2003)(2004)(2005) y del prograrna de observadores de palangre peJagico (1992)(1993)(1994)(1995)(1996)(1997)(1998)(1999)(2000)(2001)(2002)(2003)(2004)(2005) se estandarizaron por medio de Modelos Lineales Generalizados (GLMs). Las reducciones en abundancia relativa de las seis especies 0 generos de tiburones peJB.gicos que se examinaron variaron entre el 43% para IsuTUS spp. y el 88% para Prionace glauca, mientras que los descensos en abundancia relativa obtenidos del anaIisis de los datos de observadores fueron menos acentuados que los del anaIisis de los datos de los cuadernos de bit4cora, con Carcharhinus signatus y Alopias spp. mostrando tendencias positivas. No se encontraron cambios significativos en la longitud furcal de las capturas durante el periodo analizado para P. g/auca, Isurus oxyrinchus 0 C. signatus. Las tendencias obtenidas deben interpretarse con cautela debido a distintos problema...

For centuries, the mechanisms surrounding spatially complex animal migrations have intrigued scientists and the public. We present a new methodology using ocean heat content (OHC), a habitat metric that is normally a fundamental part of hurricane intensity forecasting, to estimate movements and migration of satellite-tagged marine fishes. Previous satellite-tagging research of fishes using archival depth, temperature and light data for geolocations have been too coarse to resolve detailed ocean habitat utilization. We combined tag data with OHC estimated from ocean circulation and transport models in an optimization framework that substantially improved geolocation accuracy over SST-based tracks. The OHC-based movement track provided the first quantitative evidence that many of the tagged highly migratory fishes displayed affinities for ocean fronts and eddies. The OHC method provides a new quantitative tool for studying dynamic use of ocean habitats, migration processes and responses to environmental changes by fishes, and further, improves ocean animal tracking and extends satellite-based animal tracking data for other potential physical, ecological, and fisheries applications.

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