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Tag Archives: Toronto Western Hospital

Friday Science Review: September 11, 2009

Two great medical discoveries…

Stayin’ Alive:  During a stroke, for example, neurons deprived of oxygen undergo cell death.  In a recent discovery lead by Dr. Michael Tymianski’s team at the Krembil Neuroscience Centre at Toronto Western Hospital, the protein TRPM7 was found to play a critical role in mediating this detrimental effect.   After suppressing TRPM7 expression in a localized region of a rat’s brain, they simulated a stroke by cutting off blood flow to the brain for 15 minutes.  The subsequent analysis revealed a complete lack of tissue damage compared to rat brains expressing TRPM7.  The resistance to death by cells lacking TRPM7 even preserved the brain’s cognitive function and memory performance following the ‘stroke’.  This may have tremendous implications for preventing further cell damage following ischemia in any tissue and is not necessarily limited to the brain, although it is yet to be tested elsewhere in the body

Details of the discovery are reported in the latest edition of Nature Neuroscience.

Insulin Resistance Gene Discovery: An international effort led by Dr. Robert Sladek and Dr. Constantin Polychronakos at McGill University performed a genome-wide comparison and identified a single nucleotide variation in the genetic region near the IRS1 gene that is associated with insulin resistance and hyperinsulinemia.

Dr. Sladek explains it best:

“It’s a single-nucleotide polymorphism (SNP, pronounced ‘snip’), a single letter change in your DNA,” said Sladek. “What’s interesting about this particular SNP is that it’s not linked genetically to the IRS1 gene in any way; it’s about half-a-million base-pairs away, in the middle of a genetic desert with no known genes nearby. In genetic terms, it’s halfway from Montreal to Halifax. And yet we can see that it causes a 40-per-cent reduction in the IRS1 gene, and even more important, a 40-per-cent reduction in its activity. Which means that even if insulin is present, it won’t work.”

IRS1 is known to be the key signalling protein involved in the cell’s initial response to insulin.  This recently discovered variant allele affects the level of IRS1 protein expressed and reduces the capacity of the cells to respond to insulin. Unlike other diabetes risk genes that affect insulin production in the body, this is the first that is known to suppress insulin stimulation in the cells.

The research article appears in the early online edition of Nature Genetics.

Weekend Science Review: Abba Edition

Pinky and the BrainTake a Chance on Rats:  Fiona Zeeb in Catharine Winstanley’s lab at UBC has created a rat experimental model for gambling that attracted some news coverage.  Unlike previous rat gambling experiments, this model responds to human physiological moderators of gambling behaviour, like serotonergic and dopaminergic agents, suggesting that it will be a useful system for future investigations.  Here’s the (free) full paper from this week’s Neuropsychopharmacology.

Thank You for the GWAS: A study led by Katherine Siminovich (cross-appointed (at least) at U of T, Mount Sinai and the Liver Center at Toronto Western Hospital) was published in The New England Journal of Medicine this week identifying 13 loci across the HLA class II region that were associated with primary biliary cirrhosis.

Does Your Mother Know (there’s no obvious link between fibrinolytic defects and the risk of ovarian cancer):  A PLoS One paper authored by Yaakov Bentov in Robert Casper’s lab at the Lunenfeld dismantles one widely speculated etiology of ovarian cancer.  The hypothesis — “that the inefficient removal of the blood clots and fibrin products which are deposited in the vicinity of the ovary by retrograde menstruation might be associated with an increased risk of ovarian cancer” — was not disproven, but none of the functional variants in the fibrinolytic sytem examined by Bentov et al. showed any significant association with risk of ovarian cancer.

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