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Tafazzin (TAZ) is a mitochondrial transacylase that remodels the mitochondrial cardiolipin into its mature form. Through a CRISPR screen, we identified TAZ as necessary for the growth and viability of acute myeloid leukemia (AML) cells. Genetic inhibition of TAZ reduced stemness and increased differentiation of AML cells both in vitro and in vivo. In contrast, knockdown of TAZ did not impair normal hematopoiesis under basal conditions. Mechanistically, inhibition of TAZ decreased levels of cardiolipin but also altered global levels of intracellular phospholipids, including phosphatidylserine, which controlled AML stemness and differentiation by modulating toll-like receptor (TLR) signaling., (Crown Copyright © 2019. Published by Elsevier Inc. All rights reserved.)

Background: Human biomonitoring represents an important tool for health risk assessment, supporting the characterization of contaminant exposure and nutrient status. In communities where country foods (locally harvested foods: land animals, fish, birds, plants) are integrated in the daily diet, as is the case in remote northern regions where food security is a challenge, such foods can potentially be a significant route of contaminant exposure. To assess this issue, a biomonitoring project was implemented among Dene/Métis communities of the Dehcho region of the Northwest Territories, Canada., Methods: Participants completed dietary surveys (i.e., a food frequency questionnaire and 24-h recall) to estimate food consumption patterns as well as a Health Messages Survey to evaluate the awareness and perception of contaminants and consumption notices. Biological sampling of hair, urine and blood was conducted. Toxic metals (e.g., mercury, lead, cadmium), essential metals (e.g., copper, nickel, zinc), fatty acids, and persistent organic pollutants (POPs) were measured in samples., Results: The levels of contaminants in blood, hair and urine for the majority of participants were below the available guidance values for mercury, cadmium, lead and uranium. However, from the 279 participants, approximately 2% were invited to provide follow up samples, mainly for elevated mercury level. Also, at the population level, blood lead (GM: 11 μg/L) and blood cadmium (GM: 0.53 μg/L) were slightly above the Canadian Health Measures Survey data. Therefore, although country foods occasionally contain elevated levels of particular contaminants, human exposures to these metals remained similar to those seen in the Canadian general population. In addition, dietary data showed the importance and diversity of country foods across participating communities, with the consumption of an average of 5.1% of total calories from wild-harvested country foods., Conclusion: This project completed in the Mackenzie Valley of the Northwest Territories fills a data gap across other biomonitoring studies in Canada as it integrates community results, will support stakeholders in the development of public health strategies, and will inform environmental health issue prioritization., Competing Interests: Participants provided a free consent. Ethics approval was obtained by the University of Waterloo Research Ethics Committee (#20173, #20950), the Stanton Territorial Health Authority for Human Research (29/12/2015), and the Aurora Research Institute (#15560, #15775, #15966, #15977, #16021). Health Canada ethics approval was also obtained regarding additional analysis of the biobanked samples (REB 2016–0022).Not applicable.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Traditional foods have significant nutritional, sociocultural and economic value in subarctic First Nations communities of the Northwest Territories, and play a crucial role in promoting cultural continuity and sovereignty. Omega-3 polyunsaturated fatty acids (N-3 PUFAs), including eicosapentaenoic (EPA) and docosahexaenoic acid (DHA), carry significant benefits for neurocognitive development and cardiovascular health. However, the health risks posed by methylmercury may serve to undermine the benefits of fish consumption in Northern Indigenous communities. The objective of this study was to characterize profiles for mercury (Hg) and fatty acids in fish species harvested across lakes of the Dehcho Region, in the Mackenzie Valley of the Northwest Territories, to better understand the risks and benefits associated with traditional foods. Hg levels increased with trophic position, with the highest levels found in Burbot, Lake Trout, Walleye, and Northern Pike. Lake Trout, along with planktivorous species including Lake Whitefish, Cisco, and Sucker, demonstrated higher N-3 PUFAs than other species. Negative associations were observed between Hg and N-3 PUFAs in Lake Trout, Northern Pike, Walleye and Burbot. Further stratifying these relationships revealed significant interactions by lake. Significant differences observed in fatty acid and Hg profiles across lakes underscore the importance of considering both species- and lake-specific findings. This growing dataset of freshwater fish of the Dehcho will inform future efforts to characterize human Hg exposure profiles using probabilistic dose reconstruction models., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Avocatin B, an avocado-derived compound mixture, was demonstrated recently to possess potent anticancer activity by selectively targeting and eliminating leukemia stem cells. Avocatin B is a mixture of avocadene and avocadyne, two 17-carbon polyhydroxylated fatty alcohols (PFAs), first discovered in avocado seeds; their quantities in avocado pulp are unknown. Analytical methods to detect avocado seed PFAs have utilized NMR spectroscopy and GC-MS; both of these lack quantitative capacity and accuracy. Herein, we report a sensitive LC-MS method for the quantitation of avocadene and avocadyne in avocado seed and pulp. The method has a reliable and linear response range of 0.1-50 μM (0.03-17.2 ng/μL) for both avocadene and avocadyne ( r 2 > 0.990) with a lower limit of quantitation (LLOQ) of 0.1 μM. The intra- and interassay accuracy and precision of the quality control (QC) samples at LLOQ showed ≤18.2% percentage error and ≤14.4% coefficient of variation (CV). The intra- and interassay accuracy and precision for QC samples at low and high concentrations were well below 10% error and CV. This method was successfully applied to quantify avocadene and avocadyne in total lipid extracts of Hass avocado pulp and seed matter.