Worldwide heavy oil and bitumen deposits amount to 9 trillion barrels of oil distributed in over 280 basins around the world, with Canada home to oil sands deposits of 1.7 trillion barrels. The global development of this resource and the increase in oil production from oil sands has caused environmental concerns over the presence of toxic compounds in nearby ecosystems and acid deposition. The contribution of oil sands exploration to secondary organic aerosol formation, an important component of atmospheric particulate matter that affects air quality and climate, remains poorly understood. Here we use data from airborne measurements over the Canadian oil sands, laboratory experiments and a box-model study to provide a quantitative assessment of the magnitude of secondary organic aerosol production from oil sands emissions. We find that the evaporation and atmospheric oxidation of low-volatility organic vapours from the mined oil sands material is directly responsible for the majority of the observed secondary organic aerosol mass. The resultant production rates of 45-84 tonnes per day make the oil sands one of the largest sources of anthropogenic secondary organic aerosols in North America. Heavy oil and bitumen account for over ten per cent of global oil production today, and this figure continues to grow. Our findings suggest that the production of the more viscous crude oils could be a large source of secondary organic aerosols in many production and refining regions worldwide, and that such production should be considered when assessing the environmental impacts of current and planned bitumen and heavy oil extraction projects globally.

Individuals with diabetes mellitus suffer from impaired angiogenesis and this contributes to poorer peripheral arterial disease outcomes. In experimental peripheral arterial disease, angiogenesis and perfusion recovery are impaired in mice with diabetes. We recently showed that a disintegrin and metalloproteinase domain-containing protein 12 (ADAM12) is upregulated in ischemic endothelial cells and plays a key role in post-ischemic angiogenesis and perfusion recovery following experimental peripheral arterial disease. Here we investigated the role of miR29a in the regulation of endothelial cell ADAM12 expression in ischemia and how hyperglycemia negatively affects this regulation. We also explored whether modulating miR29a can improve impaired post-ischemic angiogenesis associated with hyperglycemia. Additionally, we tested whether miR29a modulation could improve post ischemic angiogenesis in the setting of impaired vascular endothelial growth factor signaling. We forced miR29a expression in ischemic endothelial cells and assessed ADAM12 expression. We also evaluated whether hyperglycemia in vivo and in vitro impair ischemia-induced ADAM12 upregulation and miR29a downregulation. Lastly, we determined whether modulating endothelial cell miR29a expression in ischemia and hyperglycemia could improve impaired endothelial cell functions. We found under ischemic conditions where ADAM12 is upregulated in endothelial cells, miR29a is downregulated. Forced expression of miR29a in ischemic endothelial cell prevented ADAM12 upregulation . In ischemic hind limbs of mice with type 1 diabetes and in endothelial cells exposed to simulated ischemia plus hyperglycemia, ADAM12 upregulation and miR29a downregulation were blunted while angiogenesis was impaired. Knocking down miR29a with an miR29a inhibitor was sufficient to improve ADAM12 upregulation and angiogenesis in simulated ischemia plus hyperglycemia. It was also sufficient to improve perfusion recovery in type 1 diabetes mellitus mice in vivo and angiogenesis in vitro even when vascular endothelial growth factor signaling was impaired with blocking antibodies. In conclusion, MiR29a regulates endothelial cell ADAM12 upregulation in ischemia and this is impaired in hyperglycemia. Modulating miR29a improves impaired post-ischemic angiogenesis associated with hyperglycemia. Impact statement Individuals with diabetes are more likely to develop peripheral arterial disease (PAD), and when PAD is present, in those with diabetes, it is more severe and there is currently no effective medical treatment for impaired blood flow which occurs in diabetics with PAD. The current work advances the field by providing an understanding of a molecular mechanism involved in impaired post ischemic angiogenesis in diabetes. It shows for the first time that failure to downregulate miR29a in ischemic diabetic tissues is a major contributing factor to poor perfusion recovery in experimental PAD, and miR29a is elevated in skeletal muscle samples from human diabetics compared with levels in those without diabetes. Knocking down the elevated miR29a in ischemic diabetic mouse hind limbs improved perfusion recovery following experimental PAD. This shows miR29a modulation as a novel therapeutic target for improving blood flow in diabetics with PAD.

A Unified Regional Air-quality Modelling System, AURAMS, was expanded to predict six toxic volatile organic compounds (VOCs) within a continental domain and two nested domains covering eastern and western Canada. The model predictions were evaluated against Environment Canada's National Air Pollution Surveillance (NAPS) data set to assess the predictive capability of the model at daily and seasonal time scales. The predictions were also evaluated with satellite-derived column total maps for formaldehyde, carbon monoxide, and nitrogen dioxide. In general, the model showed fair to good predictive skill in terms of both correlation (R) and normalized mean bias (NMB) for benzene (R = 0.53 NMB = 26 %), formaldehyde (R = 0.73, NMB = −15 %) and acetaldehyde (R = 0.55, NMB = 29 %). For the other toxics VOCs, the model showed less predictive skill in the order 1,2,4-trimethylbenzene (R = 0.50, NMB = −41 %), 1,3-butadiene (R = 0.26, NMB = 40 %) and acrolein (R = 0.052, NMB = −51 %). The goal of this study was to apply an air quality model to assess the contribution of mobile sources to ambient levels of toxic VOCs at urban locations across Canada. The mobile source contribution varied in a complex manner for each species for different regions. For benzene and 1,2,4-trimethylbenzene, the mobile source contribution was in the range 40-65 % for major Canadian cities. The model predicted considerably lower

Background Prior studies on the role of gut-microbiome in Amyotrophic Lateral Sclerosis (ALS) pathogenesis have yielded conflicting results. We hypothesized that gut- and oral-microbiome may differentially impact two clinically-distinct ALS subtypes (spinal-onset ALS (sALS) vs. bulbar-onset ALS (bALS), driving disagreement in the field. Methods ALS patients diagnosed within 12 months and their spouses as healthy controls (n = 150 couples) were screened. For eligible sALS and bALS patients (n = 36) and healthy controls (n = 20), 16S rRNA next-generation sequencing was done in fecal and saliva samples after DNA extractions to examine gut- and oral-microbiome differences. Microbial translocation to blood was measured by blood lipopolysaccharide-binding protein (LBP) and 16S rDNA levels. ALS severity was assessed by Revised ALS Functional Rating Scale (ALSFRS-R). Results sALS patients manifested significant gut-dysbiosis, primarily driven by increased fecal Firmicutes/Bacteroidetes-ratio (F/B-ratio). In contrast, bALS patients displayed significant oral-dysbiosis, primarily driven by decreased oral F/B-ratio. For sALS patients, gut-dysbiosis (a shift in fecal F/B-ratio), but not oral-dysbiosis, was strongly associated with greater microbial translocation to blood (r = 0.8006, P < 0.0001) and more severe symptoms (r = 0.9470, P < 0.0001). In contrast, for bALS patients, oral-dysbiosis (a shift in oral F/B-ratio), but not gut-dysbiosis, was strongly associated with greater microbial translocation to blood (r = 0.9860, P < 0.0001) and greater disease severity (r = 0.9842, P < 0.0001). For both ALS subtypes, greater microbial translocation was associated with more severe symptoms (sALS: r = 0.7924, P < 0.0001; bALS: r = 0.7496, P = 0.0067). Importantly, both sALS and bALS patients displayed comparable oral-motor deficits with associations between oral-dysbiosis and severity of oral-motor deficits in bALS but not sALS. This suggests that oral-dysbiosis is not simply caused by oral/bulbar/respiratory symptoms but represents a pathological driver of bALS. Conclusions We found increasing gut-dysbiosis with worsening symptoms in sALS patients and increasing oral-dysbiosis with worsening symptoms in bALS patients. Our findings support distinct microbial mechanisms underlying two ALS subtypes, which have been previously grouped together as a single disease. Our study suggests correcting gut-dysbiosis as a therapeutic strategy for sALS patients and correcting oral-dysbiosis as a therapeutic strategy for bALS patients.

No abstract