Cumming School of Medicine
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The University of Calgary Faculty of Medicine was established in 1967 and renamed the Cumming School of Medicine in 2014. The Cumming School of Medicine is a national research leader in brain and mental health, chronic diseases and cardiovascular sciences.
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Browsing Cumming School of Medicine by Department "Biochemistry"
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Item Open Access Addressing proteolytic efficiency in enzymatic degradation therapy for celiac disease.(Scientific Reports, 2016-8-2) Rey, M.; Yang, M.L.; Lee, L.; Zhang, Y.; Sheff, J.G.; Sensen, C.W.; Mrazek, H.; Halada, P.; Man, P.; McCarville, J.L.; Verdu, E.F.; Schriemer, David C.Celiac disease is triggered by partially digested gluten proteins. Enzyme therapies that complete protein digestion in vivo could support a gluten-free diet, but the barrier to completeness is high. Current options require enzyme amounts on the same order as the protein meal itself. In this study, we evaluated proteolytic components of the carnivorous pitcher plant (Nepenthes spp.) for use in this context. Remarkably low doses enhance gliadin solubilization rates, and degrade gliadin slurries within the pH and temporal constraints of human gastric digestion. Potencies in excess of 1200:1 (substrate-to-enzyme) are achieved. Digestion generates small peptides through nepenthesin and neprosin, the latter a novel enzyme defining a previously-unknown class of prolyl endoprotease. The digests also exhibit reduced TG2 conversion rates in the immunogenic regions of gliadin, providing a twin mechanism for evading T-cell recognition. When sensitized and dosed with enzyme-treated gliadin, NOD/DQ8 mice did not show intestinal inflammation, when compared to mice challenged with only pepsin-treated gliadin. The low enzyme load needed for effective digestion suggests that gluten detoxification can be achieved in a meal setting, using metered dosing based on meal size. We demonstrate this by showing efficient antigen processing at total substrate-to-enzyme ratios exceeding 12,000:1.Item Open Access Canadian Physicians' Use of Antiobesity Drugs and Their Referral Patterns to Weight Management Programs or Providers: The SOCCER Study(Hindawi Publishing Corporation, 2010-10-15) Padwal, Raj S; Damjanovic, Suzana; Schulze, Karleen; Lewanczuk, Richard; Lau, David C.W.; Sharma, Arya MitraItem Open Access Clinical and serological evaluation of a novel CENP-A peptide based ELISA(BioMed Central, 2010-05-20) Mahler, Michael; Maes, Liesbeth; Blockmans, Daniel; Westhovens, Rene; Bossuyt, Xavier; Riemekasten, Gabriela; Schneider, Sandra; Hiepe, Falk; Swart, Andreas; Gürtler, Irmgard; Egerer, Karl; Fooke, Margrit; Fritzler, Marvin J.Item Open Access Clinical associations and potential novel antigenic targets of autoantibodies directed against rods and rings in chronic hepatitis C infection(BioMed Central, 2013-03-19) Stinton, Laura M; Myers, Robert P; Coffin, Carla S; Fritzler, Marvin JItem Open Access Consumption of diets high in prebiotic fiber or protein during growth influences the response to a high fat and sucrose diet in adulthood in rats(BioMed Central, 2010-09-29) Maurer, Alannah D.; Eller, Lindsay K.; Hallam, Megan C.; Taylor, Kim; De Bruyn (Reimer), Raylene A.Item Open Access Cysteine- rich secretory protein 3 (CRISP3), ERG and PTEN define a molecular subtype of prostate cancer with implication to patients’ prognosis(BioMed Central, 2014-03-07) Bashir, Samir Al; Alshalalfa, Mohammed; Hegazy, Samar A; Dolph, Michael; Donnelly, Bryan; Bismar, Tarek AItem Open Access DMXAA Causes Tumor Site-Specific Vascular Disruption in Murine Non-Small Cell Lung Cancer, and like the Endogenous Non-Canonical Cyclic Dinucleotide STING Agonist, 2939-cGAMP, Induces M2 Macrophage Repolarization(Public Library of Science (PLoS), 2014-06-18) Downey, Charlene M.; Aghaei, Mehrnoosh; Schwendener, Reto A.; Jirik, Frank R.Item Open Access The HLH-6 Transcription Factor Regulates C. elegans Pharyngeal Gland Development and Function(Public Library of Science, 2008-10-17) Smit, Ryan B.; Schnabel, Ralf; Gaudet, Jeffrey P.C.Item Open Access Hydra: software for tailored processing of H/D exchange data from MS or tandem MS analyses(BMC Bioinformatics, 2009-5-27) Slysz, Gordon W.; Baker, Charles A. H.; Bozsa, Benjamin M.; Dang, Anthony; Percy, Andrew J.; Bennett, Melissa; Schriemer, David C.Background Hydrogen/deuterium exchange mass spectrometry (H/DX-MS) experiments implemented to characterize protein interaction and protein folding generate large quantities of data. Organizing, processing and visualizing data requires an automated solution, particularly when accommodating new tandem mass spectrometry modes for H/DX measurement. We sought to develop software that offers flexibility in defining workflows so as to support exploratory treatments of H/DX-MS data, with a particular focus on the analysis of very large protein systems and the mining of tandem mass spectrometry data. Results We present a software package ("Hydra") that supports both traditional and exploratory treatments of H/DX-MS data. Hydra's software architecture tolerates flexible data analysis procedures by allowing the addition of new algorithms without significant change to the underlying code base. Convenient user interfaces ease the organization of raw data files and input of peptide data. After executing a user-defined workflow, extracted deuterium incorporation values can be visualized in tabular and graphical formats. Hydra also automates the extraction and visualization of deuterium distribution values. Manual validation and assessment of results is aided by an interface that aligns extracted ion chromatograms and mass spectra, while providing a means of rapidly reprocessing the data following manual adjustment. A unique feature of Hydra is the automated processing of tandem mass spectrometry data, demonstrated on a large test data set in which 40,000 deuterium incorporation values were extracted from replicate analysis of approximately 1000 fragment ions in one hour using a typical PC. Conclusion The customizable workflows and user-friendly interfaces of Hydra removes a significant bottleneck in processing and visualizing H/DX-MS data and helps the researcher spend more time executing new experiments and interpreting results. This increased efficiency will encourage the analysis of larger protein systems. The ability to accommodate the tandem MS dimension supports alternative data collection and analysis strategies, as well as higher resolution localization of deuteration where permitted by the fragmentation mechanism.Item Open Access The ING1a Tumor Suppressor Regulates Endocytosis to Induce Cellular Senescence Via the Rb-E2F Pathway(PLoS, 2013-03-05) Rajarajacholan, Uma Karthika; Thalappilly, Subhash; Riabowol, KarlItem Open Access Lactoferrin binding protein B - a bi-functional bacterial receptor protein(PLOS Pathogens, 2017-3-3) Ostan, Nicholas K. H.; Yu, Rong-Hua; Ng, Dixon; Lai, Christine Chieh-Lin; Pogoutse, Anastassia K.; Sharpe, Vladimir; Hepburn, Morgan; Sheff, Joey; Raval, Shaunak; Schriemer, David C.; Moraes, Trevor F.; Schryvers, Anthony B.Lactoferrin binding protein B (LbpB) is a bi-lobed outer membrane-bound lipoprotein that comprises part of the lactoferrin (Lf) receptor complex in Neisseria meningitidis and other Gram-negative pathogens. Recent studies have demonstrated that LbpB plays a role in protecting the bacteria from cationic antimicrobial peptides due to large regions rich in anionic residues in the C-terminal lobe. Relative to its homolog, transferrin-binding protein B (TbpB), there currently is little evidence for its role in iron acquisition and relatively little structural and biophysical information on its interaction with Lf. In this study, a combination of crosslinking and deuterium exchange coupled to mass spectrometry, information-driven computational docking, bio-layer interferometry, and site-directed mutagenesis was used to probe LbpB:hLf complexes. The formation of a 1:1 complex of iron-loaded Lf and LbpB involves an interaction between the Lf C-lobe and LbpB N-lobe, comparable to TbpB, consistent with a potential role in iron acquisition. The Lf N-lobe is also capable of binding to negatively charged regions of the LbpB C-lobe and possibly other sites such that a variety of higher order complexes are formed. Our results are consistent with LbpB serving dual roles focused primarily on iron acquisition when exposed to limited levels of iron-loaded Lf on the mucosal surface and effectively binding apo Lf when exposed to high levels at sites of inflammation.Item Open Access Micro-computed tomography-based phenotypic approaches in embryology: procedural artifacts on assessments of embryonic craniofacial growth and development(BioMed Central, 2010-02-17) Schmidt, Eric J.; Parsons, Trish E.; Jamniczky, Heather A.; Gitelman, Julian; Trpkov, Cvett; Boughner, Julia C.; Logan, C Cairine.; Sensen, Christoph W.; Hallgrímsson, BenediktItem Open Access Ndel1 promotes axon regeneration via intermediate filaments(Public Library of Science, 2008-04-23) Toth, Cory; Shim, Su Yeon; Wang, Jian; Jiang, Yulan; Neumayer, Gernot; Belzil, Camille; Liu, Wei-Qiao; Martinez, Jose; Zochodne, Douglas; Nguyen, Minh DangItem Open Access REAP: A two minute cell fractionation method(BioMed Central, 2010-11-10) Suzuki, Keiko; Bose, Pinaki; Leong-Quong, Rebecca Y. Y.; Fujita, Donald J.; Riabowol, Karl T.Item Open Access Repression of GW/P body components and the RNAi microprocessor impacts primary ciliogenesis in human astrocytes(BioMed Central, 2011-08-31) Moser, Joanna J.; Fritzler, Marvin J.; Rattner, Jerome B.Item Open Access Src Regulates the Activity of the ING1 Tumor Suppressor(PLoS, 2013-04-09) Yu, Lisa; Thakur, Satbir; Leong-Quong, Rebecca Y.Y.; Suzuki, Keiko; Pang, Andy; Bjorge, Jeffrey D.; Riabowol, Karl; Fujita, Donald J.; Fujita, Donald J.