On the statistical mechanics of prion diseases

We simulate a two-dimensional, lattice based, protein-level statistical mechanical model for prion diseases (e.g., Mad Cow disease) with concommitant prion protein misfolding and aggregation. Our simulations lead us to the hypothesis that the observed broad incubation time distribution in epidemiological data reflect fluctuation dominated growth seeded by a few nanometer scale aggregates, while much narrower incubation time distributions for innoculated lab animals arise from statistical self averaging. We model `species barriers' to prion infection and assess a related treatment protocol.Comment: 5 Pages, 3 eps figures (submitted to Physical Review Letters

The Efficacy of Tetracyclines in Peripheral and Intracerebral Prion Infection

We have previously shown that tetracyclines interact with and reverse the protease resistance of pathological prion protein extracted from scrapie-infected animals and patients with all forms of Creutzfeldt-Jakob disease, lowering the prion titre and prolonging survival of cerebrally infected animals. To investigate the effectiveness of these drugs as anti-prion agents Syrian hamsters were inoculated intramuscularly or subcutaneously with 263K scrapie strain at a 10−4 dilution. Tetracyclines were injected intramuscularly or intraperitoneally at the dose of 10 mg/kg. A single intramuscular dose of doxycycline one hour after infection in the same site of inoculation prolonged median survival by 64%. Intraperitoneal doses of tetracyclines every two days for 40 or 44 days increased survival time by 25% (doxycycline), 32% (tetracycline); and 81% (minocycline) after intramuscular infection, and 35% (doxycycline) after subcutaneous infection. To extend the therapeutic potential of tetracyclines, we investigated the efficacy of direct infusion of tetracyclines in advanced infection. Since intracerebroventricular infusion of tetracycline solutions can cause overt acute toxicity in animals, we entrapped the drugs in liposomes. Animals were inoculated intracerebrally with a 10−4 dilution of the 263K scrapie strain. A single intracerebroventricular infusion of 25 µg/ 20 µl of doxycycline or minocycline entrapped in liposomes was administered 60 days after inoculation, when 50% of animals showed initial symptoms of the disease. Median survival increased of 8.1% with doxycycline and 10% with minocycline. These data suggest that tetracyclines might have therapeutic potential for humans

Inoculation of Scrapie with the Self-Assembling RADA-Peptide Disrupts Prion Accumulation and Extends Hamster Survival

Intracerebral inoculation of 263K Scrapie brain homogenate (PrPsc) with a self-assembling RADA-peptide (RADA) significantly delayed disease onset and increased hamster survival. Time of survival was dependent on the dose of RADA and pre-incubation with PrPsc prior to inoculation. RADA treatment resulted in the absence of detectable PrPsc at 40 d followed by an increased rate of PrPsc accumulation at 75 d up to sacrifice. In all PrPsc inoculated animals, clinical symptoms were observed ∼10 d prior to sacrifice and brains showed spongiform degeneration with Congo red positive plaques. A time-dependent increase in reactive gliosis was observed in both groups with more GFAP detected in RADA treated animals at all time points. The PrP protein showed dose-dependent binding to RADA and this binding was competitively inhibited by Congo Red. We conclude that RADA disrupts the efficacy of prion transmission by altering the rate of PrPsc accumulation. This is the first demonstration that a self-assembling biomolecular peptide can interact with PrPsc, disrupt the course of Scrapie disease process, and extend survival

Etude comparative des produits d'hydrolyse enzymatique, et, catalytique du lactosérum déprotéiné sur résines échangeuses d'ions

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Recherche de descripteurs objectifs de la qualité sensorielle des pommes (Malus domestica)

Les outils instrumentaux peuvent contribuer à expliciter les caractéristiques organoleptiques des fruits déterminées par les perceptions sensorielles. L'objectif principal de ce travail est d'analyser les relations entre les paramètres sensoriels, définissant la texture et la flaveur des pommes, et les mesures instrumentales, qui caractérisent leurs propriétés mécaniques et chimiques. La première partie de l'étude concerne la validation des analyses sensorielles et instrumentales, et la caractérisation de la qualité des fruits par ces analyses. La deuxième partie porte sur la recherche des relations entre les propriétés sensorielles des pommes et les mesures instrumentales. Cette étude montre que les perception sensorielles, quoi que complexes, peuvent être reliées aux mesures instrumentales adéquates et, par conséquent, être prédites par des modèles statistiques qui tiennent compte des lois psychophysiques qui gouvernent ces perceptions.Sensory perception of fruit quality is still hard to understand and the instrumental measurements could help us to analyse it better. The principal objective of this study is to analyse the relationship between sensory perceptions, of fruit texture and flavour, and instrumental measurements, which characterise some mechanical and chemical fruit properties. The first part of the study is about a validation of sensory and instrumental measurements and characterisation of fruit quality, while the second part is about the relationship between sensory attributes of fruit quality and instrumental measurements. This study shows that sensory perception, in spite of its complexity, can be related to the appropriate instrumental measurements, and can be predicted by statistical models that take into account the psychophysical lows that control the perceptions.NANTES-BU Sciences (441092104) / SudocSudocFranceF

Détermination rapide et spécifique du taux d'hydrolyse du lactose par chromatographie liquide à haute performance à l'aide d'un étalon interne

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