Knock-Down of Cathepsin D Affects the Retinal Pigment Epithelium, Impairs Swim-Bladder Ontogenesis and Causes Premature Death in Zebrafish

The lysosomal aspartic protease Cathepsin D (CD) is ubiquitously expressed in eukaryotic organisms. CD activity is essential to accomplish the acid-dependent extensive or partial proteolysis of protein substrates within endosomal and lysosomal compartments therein delivered via endocytosis, phagocytosis or autophagocytosis. CD may also act at physiological pH on small-size substrates in the cytosol and in the extracellular milieu. Mouse and fruit fly CD knock-out models have highlighted the multi-pathophysiological roles of CD in tissue homeostasis and organ development. Here we report the first phenotypic description of the lack of CD expression during zebrafish (Danio rerio) development obtained by morpholino-mediated knock-down of CD mRNA. Since the un-fertilized eggs were shown to be supplied with maternal CD mRNA, only a morpholino targeting a sequence containing the starting ATG codon was effective. The main phenotypic alterations produced by CD knock-down in zebrafish were: 1. abnormal development of the eye and of retinal pigment epithelium; 2. absence of the swim-bladder; 3. skin hyper-pigmentation; 4. reduced growth and premature death. Rescue experiments confirmed the involvement of CD in the developmental processes leading to these phenotypic alterations. Our findings add to the list of CD functions in organ development and patho-physiology in vertebrates

The analysis of elite biathletes shooting indices in the world cup and the Olympic Games

Vytauto Didžiojo universitetasŠvietimo akademij

Metro Commuter Exposures to Particulate Air Pollution and PM2.5-Associated Elements in Three Canadian Cities: The Urban Transportation Exposure Study

System-representative commuter air pollution exposure data were collected for the metro systems of Toronto, Montreal, and Vancouver, Canada. Pollutants measured included PM2.5 (PM = particulate matter), PM10, ultrafine particles, black carbon, and the elemental composition of PM2.5. Sampling over three weeks was conducted in summer and winter for each city and covered each system on a daily basis. Mixed-effect linear regression models were used to identify system features related to particulate exposures. Ambient levels of PM2.5 and its elemental components were compared to those of the metro in each city. A microenvironmental exposure model was used to estimate the contribution of a 70 min metro commute to daily mean exposure to PM2.5 elemental and mass concentrations. Time spent in the metro was estimated to contribute the majority of daily exposure to several metallic elements of PM2.5 and 21.2%, 11.3% and 11.5% of daily PM2.5 exposure in Toronto, Montreal, and Vancouver, respectively. Findings suggest that particle air pollutant levels in Canadian metros are substantially impacted by the systems themselves, are highly enriched in steel-based elements, and can contribute a large portion of PM2.5 and its elemental components to a metro commuter's daily exposure.The authors thank the Toronto Transit Commission, la Societé ́ de transport de Montreal, and Vancouver ́ ’s Translink for their support. We would also like to thank the field technicians from Carleton and McGill University and the universities of British Columbia, Toronto, and Montreal for their diligent work. We thank Dr. Carlyn J. Matz, Hongyu You, and Marika Egyed for their contribution to this study. We thank Dr. Phil Hopke and the journal reviewers for their insightful comments. This study was funded by Health Canada

Rapid Biocompatibility Analysis of Materials via In Vivo Fluorescence Imaging of Mouse Models

Background: Many materials are unsuitable for medical use because of poor biocompatibility. Recently, advances in the high throughput synthesis of biomaterials has significantly increased the number of potential biomaterials, however current biocompatibility analysis methods are slow and require histological analysis. Methodology/Principal Findings: Here we develop rapid, non-invasive methods for in vivo quantification of the inflammatory response to implanted biomaterials. Materials were placed subcutaneously in an array format and monitored for host responses as per ISO 10993-6: 2001. Host cell activity in response to these materials was imaged kinetically, in vivo using fluorescent whole animal imaging. Data captured using whole animal imaging displayed similar temporal trends in cellular recruitment of phagocytes to the biomaterials compared to histological analysis. Conclusions/Significance: Histological analysis similarity validates this technique as a novel, rapid approach for screening biocompatibility of implanted materials. Through this technique there exists the possibility to rapidly screen large libraries of polymers in vivo.Juvenile Diabetes Research Foundation (grant 17-2007-1063

Reduced ultrafine particle levels in São Paulo’s atmosphere during shifts from gasoline to ethanol use

International audienceDespite ethanol's penetration into urban transportation, observational evidence quantifying the consequence for the atmospheric particulate burden during actual, not hypothetical, fuel-fleet shifts, has been lacking. Here we analyze aerosol, meteorological, traffic, and consumer behavior data and find, empirically, that ambient number concentrations of 7–100-nm diameter particles rise by one-third during the morning commute when higher ethanol prices induce 2 million drivers in the real-world megacity of São Paulo to substitute to gasoline use (95% confidence intervals: +4,154 to +13,272 cm −3). Similarly, concentrations fall when consumers return to ethanol. Changes in larger particle concentrations, including US-regulated PM2.5, are statistically indistinguishable from zero. The prospect of increased biofuel use and mounting evidence on ultrafines' health effects make our result acutely policy relevant, to be weighed against possible ozone increases. The finding motivates further studies in real-world environments. We innovate in using econometrics to quantify a key source of urban ultrafine particles