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Looking beyond the standard genome-wide association study: Biologically-motivated methodological approaches to discover novel genetic variants associated with complex human traits and disease
DownloadFall 2018
The standard approach for testing associations between common single nucleotide genetic variants (referred to as single nucleotide polymorphisms or SNPs) and disease entails testing disease associations for each SNP in the genome individually. This “hypothesis-free” approach has identified...
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MicroRNA Buffering and Altered Variance of Gene Expression in Response to Salmonella Infection
Download2014
Plastow, G. S., Bao, H., Kommadath, A., Guan, L. L., Tuggle, C. K., Stothard, P.
One potential role of miRNAs is to buffer variation in gene expression, although conflicting results have been reported. To investigate the buffering role of miRNAs in response to Salmonella infection in pigs, we sequenced miRNA and mRNA in whole blood from 15 pig samples before and after...
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Spring 2013
If all cells in a multicellular organism contain exactly the same genetic information, the question arises of how tissue types with distinct gene expression profiles are formed and maintained over the life of the organism. These different temporal and spatial gene expression patterns are thought...
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Fall 2019
Glioblastoma (GBM), classified as WHO grade IV astrocytoma, is the most common and lethal adult primary brain tumour. Despite recent advances in treatment, GBM prognosis remains largely unchanged with most patients succumbing to the disease within ~15 months of diagnosis. This dismal outcome can...
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Fall 2015
Malignant glioma (MG), comprised of grade III (anaplastic astrocytoma) and grade IV (glioblastoma) astrocytoma, is the most common adult brain tumour, with an incidence of ~4 in 100 000 people. Despite aggressive treatment with surgery, radiation, and chemotherapy, survival remains dismal, with...
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Phosphorylation status of 72 kDa MMP-2 determines its structure and activity in response to peroxynitrite
Download2013-01-01
Jacob-Ferreira, Anna Laura, Kondo, Marcia Yuri, Baral, Pravas Kumar, James, Michael N., Holt, Andrew, Fan, Xiaohu, Schulz, Richard
Matrix metalloproteinase-2 (MMP-2) is a key intra- and extra-cellular protease which contributes to several oxidative stress related pathologies. A molecular understanding of 72 kDa MMP-2 activity, directly mediated by S-glutathiolation of its cysteine residues in the presence of peroxynitrite...
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2016-01-01
Cai, Fangze, Li, Monica X., Pineda-Sanbria, Sandra E., Gelozia, Shorena, Lindert, Steffen, West, Frederick, Sykes, Brian D., Hwang, Peter M.
In cardiac and skeletal muscle, the troponin complex turns muscle contraction on and off in a calcium-dependent manner. Many small molecules are known to bind to the troponin complex to modulate its calcium binding affinity, and this may be useful in a broad range of conditions in which striated...
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Study of calcineurin interaction with inhibitor-1 and natural products. Towards novel calcineurin inhibitors
DownloadSpring 2012
Calcineurin (CaN) is an eukaryotic Ser/Thr protein phosphatase that plays an important role in lymphocyte activation. Inhibition of CaN leads to immune system suppression, a necessary procedure in organ transplantation. However, use of CaN inhibitors results in toxic side effects. The search for...