Le Fonds d'investissement de Montréal

monographi

La Coopérative d’habitation des Cantons de l’Est

Recherche réalisée grâce aux contributions de la Chaire de coopération Guy-Bernier et du Conseil de recherches en sciences humaines du Canada

Systems approach reveals photosensitivity and PER2 level as determinants of clock-modulator efficacy

In mammals, the master circadian clock synchronizes daily rhythms of physiology and behavior with the day-night cycle. Failure of synchrony, which increases the risk for numerous chronic diseases, can be treated by phase adjustment of the circadian clock pharmacologically, for example, with melatonin, or a CK1delta/epsilon inhibitor. Here, using in silico experiments with a systems pharmacology model describing molecular interactions, and pharmacokinetic and behavioral experiments in cynomolgus monkeys, we find that the circadian phase delay caused by CK1delta/epsilon inhibition is more strongly attenuated by light in diurnal monkeys and humans than in nocturnal mice, which are common preclinical models. Furthermore, the effect of CK1delta/epsilon inhibition strongly depends on endogenous PER2 protein levels, which differs depending on both the molecular cause of the circadian disruption and the patient\u27s lighting environment. To circumvent such large interindividual variations, we developed an adaptive chronotherapeutics to identify precise dosing regimens that could restore normal circadian phase under different conditions. Our results reveal the importance of photosensitivity in the clinical efficacy of clock-modulating drugs, and enable precision medicine for circadian disruption

Whole genome sequencing and phylogenetic analysis of \u3ci\u3eBluetongue virus\u3c/i\u3e serotype 2 strains isolated in the Americas including a novel strain from the western United States

Bluetongue is a potentially fatal arboviral disease of domestic and wild ruminants that is characterized by widespread edema and tissue necrosis. Bluetongue virus (BTV) serotypes 10, 11, 13, and 17 occur throughout much of the United States, whereas serotype 2 (BTV-2) was previously only detected in the southeastern United States. Since 1998, 10 other BTV serotypes have also been isolated from ruminants in the southeastern United States. In 2010, BTV-2 was identified in California for the first time, and preliminary sequence analysis indicated that the virus isolate was closely related to BTV strains circulating in the southeastern United States. In the current study, the whole genome sequence of the California strain of BTV-2 was compared with those of other BTV-2 strains in the Americas. The results of the analysis suggest co-circulation of genetically distinct viruses in the southeastern United States, and further suggest that the 2010 western isolate is closely related to southeastern strains of BTV. Although it remains uncertain as to how this novel virus was translocated to California, the findings of the current study underscore the need for ongoing surveillance of this economically important livestock disease

Three dimensional characterization and archiving system

This system (3D-ICAS) is being developed as a remote system to perform rapid in situ analysis of hazardous organics and radionuclide contamination on structural materials. It is in the final phase of a 3-phase program to support Decontamination and Decommissioning (D&D) operations. Accurate physical characterization of surfaces and radioactive and organic contamination is a critical D&D task. Surface characterization includes identification of dangerous inorganic materials such as asbestos and transite. 3D-ICAS robotically conveys a multisensor probe near the surfaces to be inspected, using coherent laser radar tracking, which also provides 3D facility maps. High-speed automated organic analysis is provided by means of gas chromatograph-mass spectrometer sensor which can process a sample without contact in one minute. Volatile organics are extracted directly from contaminated surfaces without sample removal; multiple stage focusing is used for high time resolution. Additional discrimination is obtained through a final stage time-of-flight mass spectrometer. The radionuclide sensors combines {alpha}, {beta}, and {gamma} counting with energy discrimination of the {alpha} channel; this quantifies isotopes of U, Pu, Th, Tc, Np, and Am in one minute. The Molecular Vibrational Spectrometry sensor is used to characterize substrate material such as concrete, transite, wood, or asbestos; this can be used to provide estimates of the depth of contamination. The 3D-ICAS will be available for real-time monitoring immediately after each 1 to 2 minute sample period. After surface mapping, 3-D displays will be provided showing contours of detected contaminant concentrations. Permanent measurement and contaminant level archiving will be provided, assuring data integrity and allowing regulatory review before and after D&D operations