Welcome Jalees Nasir (left) and Martins Oloni (right), new M.Sc. students in the lab and the McMaster Biochemistry & Biomedical Sciences graduate program. Jalees will be working on molecular epidemiological tools for surveillance of viral infections, while Martins will be collaborating with Agriculture and Agri-Food Canada (AAFC) on making our Comprehensive Antibiotic Resistance Database stronger for mobile elements involved in drug resistance in agricultural settings. Welcome Jalees & Martins!
CADMIUM EXPOSURE ALTERS GENE EXPRESSION OF LENS, RETINA, AND EYE-RELATED GENES IN ZEBRAFISH AND HUMAN LENS EPITHELIAL CELLS
Vision is a crucial aspect of life for humans and animals. Impaired vision can lead to reduced quality of life along with other complications. Cataracts are a leading cause of impaired vision and blindness worldwide. Cataracts develop as a process of aging, although several environmental and lifestyle factors increase the risk of this disease. The toxic metal cadmium (Cd) has been associated with cataract formation and other ocular diseases such as macular degeneration. Cadmium exposure exper- iments were conducted to investigate potential pathways or mechanisms by which Cd may contribute to cataract formation and ocular disease. Zebrafish larvae (72, 96, and 120 hours post fertilization), adult zebrafish (6-month male, 10-month male, and 10-month female) and the B3 human lens epithelial (HLE) cell line were acutely exposed to varying concentrations of Cd. Transcriptomic changes relative to control (0 μM Cd) were determined using microarray analysis for zebrafish larvae and RNA sequencing (RNA-Seq) for adult zebrafish and HLE cells. Gene Ontology (GO) enrichment analysis for the zebrafish larvae exposure (50 μM Cd for 4 or 8 hours) enriched the “retina development in camera-type eye” term, and genes involved in enrichment (dnmt1, ccna2, fen1, mcm3 and slbp) were down-regulated. Gene set enrichment analysis (GSEA) for the 10-month male zebrafish exposure (50 μM Cd for 4 hours) enriched the “embryonic eye morphogenesis” gene set and significant genes involved in enrichment (tcf7l1a, pitx2, fzd8a, sfrp5, lmx1bb, mfap2, six3b, lum, phactr4b, and foxc1a) were down-regulated. GSEA for the 10-month female zebrafish (50 μM Cd for 4 hours) enriched the “photoreceptor cell differentiation” gene set and significant genes involved in enrichment (odc1, thrb, and ush2a) were up-regulated. GO enrichment analysis for up-regulated genes in the HLE cell exposure (10 μM Cd for 4 hours) enriched the terms “eye development” (22 genes) and “lens development in camera-type eye” (CITED2, SKIL, CRYAB, SLC7A11, TGFB2, EPHA2, BCAR3, WNT5B, and BMP4). These results show cadmium is capable of altering transcription of eye-related genes in both zebrafish and human models, which may contribute to the formation of ocular disease. Many of these genes are involved in lens and retina development, yet they are also associated with diseases in these eye structures. Future studies could assess the consequences of altered transcription of these genes which could help elucidate the mechanisms of these changes and the overall effect of cadmium exposure on ocular disease. Ultimately, our study characterized the regulation of eye-related genes in response to Cd exposure, and provided valuable knowledge setting the foundation for identification of the molecular mechanisms contributing to ocular diseases.
McGlory C, von Allmen MT, Stokes T, Morton RW, Hector AJ, Lago BA, Raphenya AR, Smith BK, McArthur AG, Steinberg GR, Baker SK, Phillips SM
J Gerontol A Biol Sci Med Sci. 2018 Jul 9;73(8):1070-1077.
(Press release: Putting your feet up for as little as two weeks can trigger diabetic symptoms in vulnerable patients)
BACKGROUND: Physical inactivity impairs insulin sensitivity, which is exacerbated with aging. We examined the impact of 2 wk of acute inactivity and recovery on glycemic control, and integrated rates of muscle protein synthesis in older men and women.
METHODS: Twenty-two overweight, prediabetic older adults (12 men, 10 women, 69 ± 4 y) undertook 7 d of habitual activity (baseline; BL), step reduction (SR; <1,000 steps.d-1 for 14 d), followed by 14 d of recovery (RC). An oral glucose tolerance test was used to assess glycemic control and deuterated water ingestion to measure integrated rates of muscle protein synthesis.
RESULTS: Daily step count was reduced (all p < .05) from BL at SR (7362 ± 3294 to 991 ± 97) and returned to BL levels at RC (7117 ± 3819). Homeostasis model assessment-insulin resistance increased from BL to SR and Matsuda insulin sensitivity index decreased and did not return to BL in RC. Glucose and insulin area under the curve were elevated from BL to SR and did not recover in RC. Integrated muscle protein synthesis was reduced during SR and did not return to BL in RC.
CONCLUSIONS: Our findings demonstrate that 2 wk of SR leads to lowered rates of muscle protein synthesis and a worsening of glycemic control that unlike younger adults is not recovered during return to normal activity in overweight, prediabetic elderly humans.
Tsang, K.K., H. Zubyk, S. Chou, G.D. Wright, & A.G. McArthur. Decoding bad bags: Predicting antibiotic resistance phenotypes from genotype. Oral presentation at the Canadian Society of Microbiologists Annual Meeting, Winnipeg, Manitoba.
- Alcock, B., A.R. Raphenya, A.N. Sharma, K.K. Tsang, T.T.Y. Lau, A. Hernandez-Koutoucheva, & A.G. McArthur. 2018. Data and curation in the Comprehensive Antibiotic Resistance Database. Poster presentation at the Canadian Society of Microbiologists Annual Meeting, Winnipeg, Manitoba.
- Lau, T.T.Y., A.R. Raphenya, B. Alcock, & A.G. McArthur. 2018. Optimizing antimicrobial resistance surveillance tools through biological data organization and taxonomic identification of resistance genes. Poster presentation at the Canadian Society of Microbiologists Annual Meeting, Winnipeg, Manitoba.
- Maguire, F., A.R. Raphenya, B. Alcock, A.G. McArthur, F.S. Brinkman, & R.G. Beiko. 2018. The cost of speed: evaluating systematic failures in metagenomic AMR profiling. Poster presentation at the Canadian Society of Microbiologists Annual Meeting, Winnipeg, Manitoba.
- Raphenya, A.R., B. Alcock, K.K. Tsang, A.N. Sharma, T.T.Y. Lau, A. Hernandez-Koutoucheva, & A.G. McArthur. 2018. The Comprehensive Antibiotic Resistance Database and the Resistance Gene Identifier – Prediction of antimicrobial resistance genes and mutations for genomic and metagenomic sequencing data. Oral presentation at the Canadian Society of Microbiologists Annual Meeting, Winnipeg, Manitoba.
- Tsang, K.K., H. Zubyk, S. Chou, G.D. Wright, & A.G. McArthur. Decoding bad bags: Predicting antibiotic resistance phenotypes from genotype. Oral presentation at the Canadian Society of Microbiologists Annual Meeting, Winnipeg, Manitoba.
Kara Tsang passed her graduate transfer exam today, officially moving from the McMaster Biochemistry & Biomedical Sciences Masters program to the Ph.D. program. Kara’s work focusses on the intersection of biocuration, bioinformatics, machine learning, mutant screening, and phenotypic testing for prediction antimicrobial resistance phenotype from genotype. Well done Kara!
Update: Hot on the heels of becoming a Ph.D. student, Kara has won a 2018/2019 Department of Biochemistry & Biomedical Sciences’s Fred and Helen Knight Enrichment Award!
Kara Tsang wins the McMaster Faculty of Health Sciences Graduate Programs Outstanding Achievement & Excellence in Oral Presentation Awards! Her happy supervisor is honoured to win the Graduate Student Federation Excellence in Graduate Supervision Award!
Morgan TD, Graham CF, McArthur AG, Raphenya AR, Boreham DR, Manzon RG, Wilson JY, Lance SL, Howland KL, Patrick PH, Somers CM
Canadian Journal of Fisheries and Aquatic Sciences 2018 75(6):836-849.
Round whitefish (Prosopium cylindraceum) have a broad, disjunct range across northern North America and Eurasia, and little is known about their genetic population structure. We performed genetic analyses of round whitefish from 17 sites across its range using nine microsatellites, two mitochondrial DNA (mtDNA) loci, and 4918 to 8835 single-nucleotide polymorphism (SNP) loci. Our analyses identified deep phylogenetic division between eastern and western portions of the range, likely indicative of origins from at least two separate Pleistocene glacial refugia. Regionally, microsatellites and SNPs identified congruent patterns in subdivision, and population structure was consistent with expectations based on hydrologic connectivity. Within the Laurentian Great Lakes, Lake Huron and Lake Ontario were identified as key areas of interest. Lake Huron appears to be a contemporary source population for several other Great Lakes, and Lake Ontario contains a genetically discrete group of round whitefish. In all cases, multiple genetic markers yielded similar patterns, but SNPs offered substantially enhanced resolution. We conclude that round whitefish have population subdivision on several scales important for understanding their evolutionary history and conservation planning.
Tammy Lau has been awarded a prestigious Michael G. DeGroote Institute for Infectious Disease Research (IIDR) Summer Student Fellowship for her work on development of k-mer approaches to predicting pathogen-of-origin for metagenomics antimicrobial resistance gene sequences. More details here.
Congratulations Tammy!