Activité in vivo d'un plasmide recombinant contenant un tandem de deux génomes du virus du polyome

L'intérêt que nous portons à la relation existant entre la transformation néoplasique par le virus du polyome et le mode d'intégration du génome viral dans l'ADN cellulaire nous a amenés à construire une série de molécules multimériques à partir de plasmides recombinants encodant différentes portions du génome viral. Les plasmides multimériques ont été obtenus par l'intermédiaire du système de recombinaison de différentes souches bactériennes. L'introduction des unités monomériques dans la souche bactérienne E. coli X-1776, qui est rec+, nous a permis d'obtenir des molécules oligomériques. Ces dernières ont été stabilisées dans la souche rec A- HB101, avant d'être caractérisées. Les multimères obtenus contiennent un nombre entier de copies de l'unité de départ qui sont liées entre elles en tandem tête à queue. La fréquence d'obtention d'un multimère donné est d'autant plus faible que le nombre de copies de l'unité de départ qu'il contient est élevé. De plus, la technique utilisée ne nous a pas permis d'obtenir de molécule de plus de 20 Kb. C'est donc dire que plus un plasmide monomérique est petit, plus le nombre maximal de copies que l'on puisse en obtenir dans un multimère est élevé. Par modification d'une des molécules multimériques obtenues, nous avons produit un recombinant contenant un tandem de deux copies complètes du génome viral lié au plasmide pBR322. Le potentiel tumorigène de cette molécule (pPB22) a été évalué chez les rats nouveaux-nés et s'est avéré comparable à celui de recombinants ne contenant qu'une copie du génome viral ou que la portion proximale de sa région précoce. Comme dans le cas de tumeurs induites avec une seule copie du génome viral, les lignées tumorales induites par pPB22 ne peuvent produire l'antigène grand T. Ceci rend encore plus plausible, l'hypothèse qui avait déjà été émise et selon laquelle il y aurait sélection in vivo contre les cellules produisant cette protéine virale. Suite à l'injection de pPB22 à des souris nues, la souris étant l'hôte naturel de polyome, nous avons pu détecter la production de génomes viraux libres dans les reins des animaux. Cette production s'est même manifestée chez un des animaux injectés, par l'apparition des symptômes liés à une infection par le virus du polyome. Les génomes viraux seraient apparus chez les animaux suite à un événement de recombinaison intramoléculaire impliquant le recombinant pPB22. L'environnement permissif fourni par les souris aurait assuré la réplication des génomes viraux ainsi libérés

Principles and Operational Parameters to Optimize Poison Removal with Extracorporeal Treatments

A role for nephrologists in the management of a poisoned patient involves evaluating the indications for, and methods of, enhancing the elimination of a poison. Nephrologists are familiar with the various extracorporeal treatments ( ECTR s) used in the management of impaired kidney function, and their respective advantages and disadvantages. However, these same skills and knowledge may not always be considered, or applicable, when prescribing ECTR for the treatment of a poisoned patient. Maximizing solute elimination is a key aim of such treatments, perhaps more so than in the treatment of uremia, because ECTR has the potential to reverse clinical toxicity and shorten the duration of poisoning. This manuscript reviews the various principles that govern poison elimination by ECTR (diffusion, convection, adsorption, and centrifugation) and how components of the ECTR can be adjusted to maximize clearance. Data supporting these recommendations will be presented, whenever available.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/108055/1/sdi12247.pd

Hair Manganese and Hyperactive Behaviors: Pilot Study of School-Age Children Exposed through Tap Water

BACKGROUND: Neurotoxic effects are known to occur with inhalation of manganese particulates, but very few data are available on exposure to Mn in water. We undertook a pilot study in a community in Québec (Canada) where naturally occurring high Mn levels were present in the public water system. Our objective was to test the hypothesis that greater exposure to Mn via drinking water would be reflected in higher Mn content in hair which, in turn, would be associated with increased level of hyperactive behaviors. METHODS: Forty-six children participated in the study, 24 boys and 22 girls, 6–15 years of age (median, 11 years). Their homes received water from one of two wells (W) with different Mn concentrations: W1: mean 610 μg/L; W2: mean 160 μg/L. The Revised Conners’ Rating Scale for parents (CPRS-R) and for teachers (CTRS-R) were administered, providing T-scores on the following subscales: Oppositional, Hyperactivity, Cognitive Problems/Inattention, and ADHD Index. RESULTS: Children whose houses were supplied by W1 had higher hair Mn (MnH) than those supplied by W2 (mean 6.2 ± 4.7 μg/g vs. 3.3 ± 3.0 μg/g, p = 0.025). MnH was significantly associated with T-scores on the CTRS-R Oppositional (p = 0.020) and Hyperactivity (p = 0.002) subscales, after adjustment for age, sex, and income. All children with Oppositional and Hyperactivity T-scores ≥ 65 had MnH > 3.0 μg/g. CONCLUSIONS: The findings of this pilot study are sufficiently compelling to warrant more extensive investigations into the risks of Mn exposure in drinking water

Development of optimised tissue-equivalent materials for proton therapy

OBJECTIVE: In proton therapy there is a need for proton optimised tissue-equivalent materials as existing phantom materials can produce large uncertainties in the determination of absorbed dose and range measurements. The aim of this work is to develop and characterise optimised tissue-equivalent materials for proton therapy. APPROACH: A mathematical model was developed to enable the formulation of epoxy-resin based tissue-equivalent materials that are optimised for all relevant interactions of protons with matter, as well as photon interactions, which play a role in the acquisition of CT numbers. This model developed formulations for vertebra bone- and skeletal muscle-equivalent plastic materials. The tissue equivalence of these new materials and commercial bone- and muscle-equivalent plastic materials were theoretical compared against biological tissue compositions. The new materials were manufactured and characterised by their mass density, relative stopping power (RSP) measurements, and CT scans to evaluate their tissue-equivalence. MAIN RESULTS: Results showed that existing tissue-equivalent materials can produce large uncertainties in proton therapy dosimetry. In particular commercial bone materials showed to have a relative difference up to 8 % for range. On the contrary, the best optimised formulations were shown to mimic their target human tissues within 1-2 % for the mass density and RSP. Furthermore, their CT-predicted RSP agreed within 1-2 % of the experimental RSP, confirming their suitability as clinical phantom materials. SIGNIFICANCE: We have developed a tool for the formulation of tissue-equivalent materials optimised for proton dosimetry. Our model has enabled the development of proton optimised tissue-equivalent materials which perform better than existing tissue-equivalent materials. These new materials will enable the advancement of clinical proton phantoms for accurate proton dosimetry

Social support, but not perceived food environment, is associated with diet quality in French-speaking Canadians from the PREDISE study

The objectives were to assess whether social support for healthy eating and perceived food environment are associated with diet quality, and to investigate if sociodemographic characteristics moderate these associations. A probability sample of French-speaking adults from the Province of Québec, Canada, was recruited in the context of the PREDISE study. Participants reported their perceptions of supportive and non-supportive actions related to healthy eating from close others at home and outside of home (n = 952), and of the accessibility to healthy foods (n = 1035). The Canadian Healthy Eating Index (C-HEI) was calculated based on three Web-based 24 h food recalls. Multiple linear regression models showed that supportive (B = 1.50 (95% CI 0.46, 2.54)) and non-supportive (B = −3.06 (95% CI −4.94, −1.18)) actions related to healthy eating from close others at home were positively and negatively associated with C-HEI, respectively, whereas actions from close others outside of home were not. The negative association between non-supportive actions occurring at home and C-HEI was stronger among participants with lower (vs. higher) levels of education (p interaction = 0.03). Perceived accessibility to healthy foods was not associated with C-HEI (p > 0.05). These results suggest that the social environment may have a stronger influence on healthy eating than the perceived physical environment. This adds support for healthy eating promotion programs involving entire families, especially for more socioeconomically disadvantaged individuals, whose efforts to eat healthily may be more easily thwarted by non-supportive household

Associations between cardiorespiratory fitness, physical activity and clustered cardiometabolic risk in children and adolescents: the HAPPY study

Clustering of cardiometabolic risk factors can occur during childhood and predisposes individuals to cardiometabolic disease. This study calculated clustered cardiometabolic risk in 100 children and adolescents aged 10-14 years (59 girls) and explored differences according to cardiorespiratory fitness (CRF) levels and time spent at different physical activity (PA) intensities. CRF was determined using a maximal cycle ergometer test, and PA was assessed using accelerometry. A cardiometabolic risk score was computed as the sum of the standardised scores for waist circumference, blood pressure, total cholesterol/high-density lipoprotein ratio, triglycerides and glucose. Differences in clustered cardiometabolic risk between fit and unfit participants, according to previously proposed health-related threshold values, and between tertiles for PA subcomponents were assessed using ANCOVA. Clustered risk was significantly lower (p < 0.001) in the fit group (mean 1.21 ± 3.42) compared to the unfit group (mean -0.74 ± 2.22), while no differences existed between tertiles for any subcomponent of PA. Conclusion These findings suggest that CRF may have an important cardioprotective role in children and adolescents and highlights the importance of promoting CRF in youth

The circumpolar impacts of climate change and anthropogenic stressors on Arctic cod (Boreogadus saida) and its ecosystem

Arctic cod biomass are predicted. In most Arctic seas, the relative abundance of Arctic cod within the fish community will likely fluctuate in accordance with cold and warm periods. A reduced abundance of Arctic cod will negatively affect the abundance, distribution, and physiological condition of certain predators, whereas some predators will successfully adapt to a more boreal diet. Regional management measures that recognize thecritical roleof Arcticcod arerequiredtoensure that increased anthropogenic activities do not exacerbate the impacts of climate change on Arctic marine ecosystems. Ultimately, the mitigation of habitat loss for Arctic cod will only be achieved through a global reduction in carbon emissions